Retinoids. Topical retinoids are considered the first-line treatment option for acne. They work by normalizing some of the main contributors to comedo formation: hyperproliferation of keratinocytes and corneocyte cohesion. By normalizing the desquamation process of the epithelium, comedone formation is decreased and existing comedones are expelled. Retinoids also have anti-inflammatory properties owing to their ability to decrease the expression of TLRs and proinflammatory mediators. This makes them an acceptable form of monotherapy for both comedonal and inflammatory lesions. In addition, they assist in the penetration of other topical medications, which is why they are commonly combined with other products such as benzoyl peroxide and topical antibacterials.²,³,⁴

Topical retinoids used today include tretinoin (all-trans-retinoic acid), adapalene, and tazarotene. Tretinoin is a naturally occurring metabolite of retinol and was the first topical retinoid used for acne treatment. It works by binding in the skin to both retinoic acid receptors α (RARα) and γ (RARγ). Common concentrations prescribed are 0.025%, 0.05%, and 0.1%, and they come in cream or gel vehicles. Tretinoin is photolabile and therefore should be applied at night. It typically takes around
2 to 3 months to observe improvement and is pregnancy category C. Adapalene is a newer, synthetic retinoid that binds only to RARγ, making it less irritating than tretinoin. It comes in 0.1% and 0.3% formulations, can be applied morning or night, and is pregnancy category C. Although previously only available via prescription, the 0.1% formulation recently became US Food and Drug Administration (FDA) approved to be sold over the counter. Tazarotene is another synthetic topical retinoid that, like adapalene, selectively binds only RARγ. Even though its mechanism of action is similar, it is considered much stronger than adapalene, which also makes it more irritating. It comes in cream or gel formulations of 0.05% and 0.1% concentrations and is pregnancy category X. The main side effects observed in all retinoids is local skin irritation, erythema, and dryness, which can be lessened with every other day application, if needed, and moisturizers.²,³,⁷

Benzoyl Peroxide. Benzoyl peroxide is a topical over-the-counter treatment that has been used for years and is considered by some providers to be a first-line treatment. It works as an antibacterial against P acnes and therefore seems to be more efficacious for inflammatory lesions compared with comedonal lesions. The advantage of using benzoyl peroxide is that there is no risk of P acnes resistance, and it can be combined with many other topical medications. Treatment is usually
once or twice daily, and preparations are made in 2.5% to 10% concentrations. It is pregnancy category C, and common side effects are local skin irritation and peeling. Of note, it is important to remind patients that this medication will bleach fabric, so washing hands thoroughly after usage, allowing it time to dry on the skin, and using white sheets and towels is recommended.²,³,⁴,⁶,⁷

Antibacterials. Topical antibacterials include the macrolides, clindamycin and erythromycin, and dapsone. They are indicated for mild to moderate acne and come in a variety of formulations. Clindamycin comes in many vehicles such as gel, lotion, solution, and foam and is prescribed in a 1% concentration. Erythromycin is used in a 2% concentration as a gel or solution. They are both pregnancy category B. Owing to the risk of antibiotic resistance, benzoyl peroxide should be used with these topical antibacterials for reasons previously mentioned. These can also be used with topical retinoids.²,³,⁴

Dapsone is a newer topical antibacterial that comes in gel formulations of 5% and 7.5% and is applied twice or once daily, respectively. It is pregnancy category C, and side effects include local skin irritation, mild pruritus, burning, hemolytic anemia, and yellow-orange discoloration of the skin when concomitantly used with benzoyl peroxide.²,³,⁷

Salicylic Acid and Azelaic Acid. Salicylic acid is a commonly used over-the-counter acne treatment found in up to 2% concentrations in acne washes, toners, and pads. It has mild anti-inflammatory action and is also a mild irritant, which helps to dry up lesions. Side effects are mild irritation, erythema, and scaling, and it is pregnancy category C.²,³

Azelaic acid is a dicarboxylic acid that can be effective for both mild inflammatory and comedonal acne. It is available as a 15% gel or foam and as a 20% cream and has anti-inflammatory, antimicrobial, and comedolytic properties. It is typically better tolerated than retinoids, may help to lighten postinflammatory hyperpigmentation, and is pregnancy category B.²,³,⁷

Oral Antibiotics. Oral antibiotics have been used for decades for the treatment of moderate to severe acne. They are typically reserved for individuals with inflammatory acne, those who scar easily, those with truncal acne, and for those who do not respond to topical treatment. The most commonly prescribed antibiotics are the tetracycline derivatives, doxycycline and minocycline. These antibiotics not only inhibit the growth of P acnes but also are mainly used for their anti-inflammatory effects as well. They are dosed at 50 to 100 mg once or twice daily. The goal of therapy is to initiate patients at a high dose and decrease until they can be maintained on topical therapy. It can take up to 8 to 12 weeks to observe efficacy, and patients typically remain on therapy for 4 to 6 months. The side effect specific to doxycycline is photosensitivity; therefore, patients should be cautious in the sunlight owing to easier risk of sunburn. Also, gastrointestinal side effects are commonly observed, so patients should be instructed not to take their medication before bedtime and to swallow it with a full glass of water. Possible adverse effects of minocycline are vertigo, lupuslike syndromes, and gray-blue pigmentation in areas of inflammation, such as the teeth, gums, nails, scars, and shins. Both of these antibiotics are pregnancy category D and can stain growing teeth, which is why they are prescribed only for children greater than 8 years of age. When the tetracyclines cannot be prescribed, amoxicillin is another alternative that is safe in pregnancy, generally prescribed at 250 to 500 mg daily to up to 3 times per day. With all oral antibiotic usage, it is recommended to use topical benzoyl peroxide to decrease the risk of antibiotic resistance.²,³,⁴,⁷

Hormonal Therapy. Hormonal therapy can be very effective when treating acne in females and is generally used as a second-line treatment. It is especially useful in adult women who have acne located on the lower face and those whose acne worsens around their menstrual cycle. The main classes of medications used to treat hormonal acne are oral contraceptives and spironolactone, and they both work as antiandrogens. Oral contraceptives are effective because they block both ovarian and adrenal production of androgens. Medications such as Ortho Tri-Cyclen, Yaz, Yasmin, Estrostep, and Alesse all have proven to be effective in acne. Side effects such as nausea, abnormal menses, weight gain, breast tenderness, melasma, and increased risk of blood clots are all factors to consider when initiating treatment.²,³

Spironolactone, an aldosterone receptor antagonist, is not only used as an antihypertensive but is also effective for treating hormonal acne. It works as an androgen receptor blocker and is typically dosed at 100 mg daily, but effective doses range from 25 to 200 mg per day. Owing to feminization of the male fetus during
pregnancy, it is strongly recommended that an effective form of birth control be used with spironolactone. Other side effects are breast tenderness, headache, diuresis, dizziness, fatigue, and hyperkalemia.²,³,⁷

Isotretinoin. Oral isotretinoin (13-cis-retinoic acid) is one of the most effective treatments for acne and has been prescribed for over 25 years. It is the only medication approved by the FDA for severe cystic acne; however, providers also use it in patients with moderate to severe acne that is resistant to all other forms of treatment. After 1 course, which takes an average of 4 to 6 months, most patients can expect around an 85% improvement in their acne.¹ It is dosed at 0.5 to 1 mg/kg/d taken in 1 dose or divided into 2 daily doses. It is recommended to be taken with a fatty meal to increase absorption. To obtain prolonged remission, the goal is to reach a cumulative dose of 120 to 150 mg/kg by the end of treatment. The advantage to using isotretinoin is that, in the majority of patients, remission can last years and patients can remain acne free through early adulthood. Isotretinoin therapy is not without risks and has more side effects than other acne medications. First and foremost, isotretinoin is pregnancy category X and can cause severe fetal abnormalities. Its usage is heavily regulated by the FDA (through the iPLEDGE management program), which requires monthly visits by the patient to their dermatologist during treatment. Women should use an effective form of birth control and should not become pregnant until 1 month after stopping the medication. Other disorders, such as depression and inflammatory bowel disease, have been linked to isotretinoin therapy but this connection remains controversial. Abnormal laboratory values, such as elevated lipids and liver enzymes, can occur, so regular laboratory tests are performed to monitor these changes closely. More common but less severe side effects are dose dependent and include dry skin, dry lips, dry eyes, and dry oronasal mucosa, which occur in 90% of patients.²,³,⁴,⁵