Efforts to better understand the mechanisms of sebum production are underway. The aim of this research is to develop medications that target and interfere with the hormones that are known to increase sebum production (e.g., IGF-1 and alpha-melanocyte-stimulating hormone). Additional sebum-lowering medications being researched include topical antiandrogens and peroxisome proliferator-activated receptor modulators. Another avenue of early-stage research has focused on how to best use laser and light therapy to selectively destroy sebum-producing glands in the skin's hair follicles in order to reduce sebum production and improve acne appearance.
Frequently used topical retinoids include adapalene, isotretinoin, retinol, tazarotene, and tretinoin. They often cause an initial flare-up of acne and facial flushing, and can cause significant skin irritation. Generally speaking, retinoids increase the skin's sensitivity to sunlight and are therefore recommended for use at night. Tretinoin is the least expensive of the topical retinoids and is the most irritating to the skin, whereas adapalene is the least irritating to the skin but costs significantly more. Most formulations of tretinoin cannot be applied at the same time as benzoyl peroxide. Tazarotene is the most effective and expensive topical retinoid, but is not as well-tolerated. Retinol is a form of vitamin A that has similar but milder effects, and is used in many over-the-counter moisturizers and other topical products.
For UVA protection, a sunscreen with a high UVA protection of PA+++ or higher of PA++++ as recommended, especially to treat PIE. PPD is the UVA equivalent of SPF; use a sunscreen with a minimum of PPD20. The PA+ system has a + that corresponds to a tier of PPD protection. Of note, different countries use different PA systems. Japan and Taiwan changed their PA system to a 4+ tier system while Korea uses a 3+ tier system.
Topical antibiotics deemed safe during pregnancy include clindamycin, erythromycin, and metronidazole (all category B), due to negligible systemic absorption. Nadifloxacin and dapsone (category C) are other topical antibiotics that may be used to treat acne in pregnant women, but have received less study. No adverse fetal events have been reported from the topical use of dapsone. If retinoids are used there is a high risk of abnormalities occurring in the developing fetus; women of childbearing age are therefore required to use effective birth control if retinoids are used to treat acne. Oral antibiotics deemed safe for pregnancy (all category B) include azithromycin, cephalosporins, and penicillins. Tetracyclines (category D) are contraindicated during pregnancy as they are known to deposit in developing fetal teeth, resulting in yellow discoloration and thinned tooth enamel. Their use during pregnancy has been associated with development of acute fatty liver of pregnancy and is further avoided for this reason.
Hydroquinone lightens the skin when applied topically by inhibiting tyrosinase, the enzyme responsible for converting the amino acid tyrosine to the skin pigment melanin, and is used to treat acne-associated postinflammatory hyperpigmentation. By interfering with new production of melanin in the epidermis, hydroquinone leads to less hyperpigmentation as darkened skin cells are naturally shed over time. Improvement in skin hyperpigmentation is typically seen within six months when used twice daily. Hydroquinone is ineffective for hyperpigmentation affecting deeper layers of skin such as the dermis. The use of a sunscreen with SPF 15 or higher in the morning with reapplication every two hours is recommended when using hydroquinone. Its application only to affected areas lowers the risk of lightening the color of normal skin but can lead to a temporary ring of lightened skin around the hyperpigmented area. Hydroquinone is generally well-tolerated; side effects are typically mild (e.g., skin irritation) and occur with use of a higher than the recommended 4% concentration. Most preparations contain the preservative sodium metabisulfite, which has been linked to rare cases of allergic reactions including anaphylaxis and severe asthma exacerbations in susceptible people. In extremely rare cases, repeated improper topical application of high-dose hydroquinone has been associated with an accumulation of homogentisic acid in connective tissues, a condition known as exogenous ochronosis.
Diet. Studies indicate that certain dietary factors, including skim milk and carbohydrate-rich foods — such as bread, bagels and chips — may worsen acne. Chocolate has long been suspected of making acne worse. A small study of 14 men with acne showed that eating chocolate was related to a worsening of symptoms. Further study is needed to examine why this happens and whether people with acne would benefit from following specific dietary restrictions.