Acne Vulgaris

1. 1. Adebamowo CA, Spiegelman D, Berkey CS, et al: Milk consumption and acne in teenaged boys. J Am Acad Dermatol 58(5):787-793, 2008. doi: 10.1016/j.jaad.2007.08.049

2. 2. Smith RN, Mann NJ, Braue A, et al: The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: A randomized, investigator-masked, controlled trial. J Am Acad Dermatol 57(2):247-256, 2007. doi: 10.1016/j.jaad.2007.01.046

3. 3. Vora S, Ovhal A, Jerajani H, et al: Correlation of facial sebum to serum insulin-like growth factor-1 in patients with acne. Br J Dermatol 159(4):990-991, 2008. doi: 10.1111/j.1365-2133.2008.08764.x

4. 4. Nagpal M, De D, Handa S, et al: Insulin resistance and metabolic syndrome in young men with acne. JAMA Dermatol 152(4):399-404, 2016. doi: 10.1001/jamadermatol.2015.4499

Treatment of mild acne should be continued for 6 to 12 weeks or until lesions respond. Maintenance treatment is usually necessary to maintain control.

Single-agent therapy is generally sufficient for comedonal acne. A mainstay of treatment for comedones is daily topical tretinoin as tolerated. Daily adapalene gel, tazarotene cream or gel, azelaic acid cream, and glycolic or salicylic acid are alternatives for patients who cannot tolerate topical tretinoin. Adverse effects include erythema, burning, stinging, and peeling. Adapalene and tazarotene are retinoids; like tretinoin, they tend to be somewhat irritating and photosensitizing. Azelaic acid has comedolytic and antibacterial properties by an unrelated mechanism and may be synergistic with retinoids.

Dual therapy (eg, a combination of tretinoin with benzoyl peroxide, a topical antibiotic, or both) should be used to treat mild papulopustular (inflammatory) acne. The topical antibiotic is usually erythromycin or clindamycin. Combining benzoyl peroxide with these antibiotics can help limit development of resistance. Glycolic acid may be used instead of or in addition to tretinoin but is no longer used commonly. Treatments have no significant adverse effects other than drying and irritation (and rare allergic reactions to benzoyl peroxide).

Physical extraction of comedones using a comedone extractor is an option for patients unresponsive to topical treatment. Comedone extraction may be done by a physician, nurse, or physician assistant. One end of the comedone extractor is like a blade or bayonet that punctures the closed comedone. The other end exerts pressure to extract the comedone.

Oral antibiotics (eg, tetracycline, minocycline, doxycycline, erythromycin) can be used when wide distribution of lesions makes topical therapy impractical.

Clascoterone is the first topical androgen receptor inhibitor for the treatment of acne. It can be used in patients 12 years of age and older. Clascoterone 1% cream is applied 2 times a day. Adverse effects include redness, scaling or dryness, and itching; although hyperkalemia and hypothalamic-pituitary-adrenal axis suppression have been predicted based on its mechanism, these effects have not been noticed clinically (7).

Oral systemic therapy with antibiotics is the best way to treat moderate acne. Antibiotics effective for acne include tetracycline, minocycline, erythromycin, doxycycline, and sarecycline. Full benefit takes ≥ 12 weeks.

Topical therapy as for mild acne is usually used concomitantly with oral antibiotics.

Doxycycline and minocycline are first-line medications; both can be taken with food. Tetracycline is also reasonable, but it cannot be taken with food and may have lower efficacy than doxycycline and minocycline. Doxycycline and minocycline dosage is 50 to 100 mg orally 2 times a day. Doxycycline may cause photosensitivity, and minocycline may have more adverse effects with chronic use, including drug-induced lupus and hyperpigmentation. To reduce the development of antibiotic resistance after control is achieved (usually 2 to 3 months), the dose is tapered as much as possible to maintain control. Sarecycline is a newer tetracycline antibiotic. Antibiotics may be discontinued if topical therapy maintains control.

Erythromycin and azithromycin are other options, but they are more likely to cause gastrointestinal adverse effects and antibiotic resistance develops more often. Some physicians also use sulfamethoxazole/trimethoprim, SMX-TMP, Cotrimoxazole. However, antibacterial resistance may develop, and this combination can cause rare adverse drug reactions.

Long-term use of antibiotics may cause a gram-negative pustular folliculitis around the nose and in the center of the face. This uncommon superinfection may be difficult to clear and is best treated with oral isotretinoin after discontinuing the oral antibiotic. Ampicillin is an alternative treatment for gram-negative folliculitis. In women, prolonged antibiotic use can cause candidal vaginitis; if local and systemic therapy does not eradicate this problem, antibiotic therapy for acne must be stopped.

If the patient is female and unresponsive to oral antibiotics, a trial of oral antiandrogens (combined oral contraceptives and/or spironolactone) may be considered.

Oral isotretinoin is the best treatment for patients with moderate acne in whom antibiotics are unsuccessful and for those with severe inflammatory acne. Dosage of isotretinoin is usually 1 mg/kg once a day for 16 to 20 weeks, but the dosage may be increased to 2 mg/kg once a day. If adverse effects make this dosage intolerable, it may be reduced to 0.5 mg/kg once a day. After therapy, acne may continue to improve.

Many patients do not require a second course of treatment; when needed, it is resumed only after the medication has been stopped for 4 (a few) months, except in severe cases when it may be resumed earlier. Retreatment is required more often if the initial dosage is low (0.5 mg/kg). With this dosage (which is very popular in Europe), fewer adverse effects occur, but prolonged therapy is usually required. Cumulative dosing has gained support; a total dosage of 120 to 150 mg/kg resulted in lower recurrence rates, and some experts suggest a higher cumulative dose of 220 mg/kg (8).

Isotretinoin is nearly always effective, but use is limited by adverse effects, including dryness of conjunctivae and mucosae of the genitals, chapped lips, arthralgias, depression, elevated lipid levels, and the risk of birth defects if treatment occurs during pregnancy. Hydration with water followed by petrolatum application usually alleviates mucosal and cutaneous dryness. Arthralgias (mostly of large joints or the lower back) often occur. Increased risk of depression and suicide is much publicized but probably rare. Although risk of new or worsened inflammatory bowel disease (Crohn disease and ulcerative colitis) has been proposed to be associated with use of isotretinoin, such an association now appears unlikely (9).

Complete blood count, liver tests, triglyceride, and cholesterol levels should be determined before treatment. Each should be reassessed at 4 weeks and, unless abnormalities are noted, need not be repeated until the end of treatment. Triglycerides rarely increase to a level at which the medication should be stopped. Liver function is seldom affected. Because isotretinoin is teratogenic, women of childbearing age are told that they are required to use 2 methods of contraception for 1 month before treatment, during treatment, and for at least 1 month after stopping treatment. Pregnancy tests should be done before beginning therapy and monthly until 1 month after therapy stops.

Intralesional injection of 0.1 mL triamcinolone acetonide suspension 2.5 mg/mL (the 10 mg/mL suspension must be diluted) is indicated for patients with firm (cystic) acne who seek quick clinical improvement with reduced scarring. Local atrophy may occur but is usually transient. For isolated, very boggy lesions, incision and drainage are often beneficial but may result in residual scarring.

Pyoderma faciale is treated with oral corticosteroids and isotretinoin.

Acne fulminans is commonly treated with oral corticosteroids and systemic antibiotics.

Acne conglobata is treated with oral isotretinoin and systemic corticosteroids if severe and if systemic antibiotics fail.

For acne caused by endocrine abnormalities (eg, polycystic ovary syndrome, virilizing adrenal tumors in females), antiandrogens are indicated. Spironolactone, which has some antiandrogen effects, is sometimes prescribed to treat acne. Cyproterone acetate is used in Europe. When other measures fail, an estrogen/progestin–containing contraceptive may be tried; therapy ≥ 6 months is needed to evaluate effect.

Small scars can be treated with chemical peels, laser resurfacing, or dermabrasion. Deeper, discrete scars can be excised. Wide, shallow depressions can be treated with subcision or injection of collagen or another filler. Fillers, including collagen, hyaluronic acid, and polymethylmethacrylate, are temporary and must be repeated periodically.

1. 1. Dall'Oglio F, Nasca M, Fiorentini F, Micali G: Diet and acne: Review of the evidence from 2009 to 2020. Int J Dermatol 60(6):672–685, 2021. doi: 10.1111/ijd.15390 

2. 2. Koltun W, Maloney JM, Marr J, et al: Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3 mg administered in a 24/4 regimen: a pooled analysis. Eur J Obstet Gynecol Reprod Biol 2011 Apr;155(2):171-5. doi: 10.1016/j.ejogrb.2010.12.027. Epub 2011 Feb 2.

3. 3. Grandhi R, Alikhan A: Spironolactone for the Treatment of Acne: A 4-Year Retrospective Study. Dermatology 233(2-3):141-144, 2017. doi: 10.1159/000471799

4. 4. Roberts EE, Nowsheen S, Davis MDP, et al: Treatment of acne with spironolactone: A retrospective review of 395 adult patients at Mayo Clinic, 2007-2017. J Eur Acad Dermatol Venereol 34(9):2106-2110, 2020. doi: 10.1111/jdv.16302

5. 5. Barbaric J, Abbott R, Posadzki P, et al: Light therapies for acne. Cochrane Database Syst Rev 9(9):CD007917, 2016. doi: 10.1002/14651858.CD007917.pub2

6. 6. Bienenfeld A, Nagler AR, Orlow SJ: Oral antibacterial therapy for acne vulgaris: An evidence-based review. Am J Clin Dermatol 18(4):469–490, 2017. doi: 10.1007/s40257-017-0267-z

7. 7. Hebert A, Thiboutot D, Stein Gold L, et al: Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: Two phase 3 randomized clinical trials. JAMA Dermatol 156(6):621–630, 2020. doi:10.1001/jamadermatol.2020.0465

8. 8. Blasiak RC, Stamey CR, Burkhart CN, et al: High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol 149(12):1392–1398, 2013. doi: 10.1001/jamadermatol.2013.6746

9. 9. Lee SY, Jamal MM, Nguyen ET, et al: Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. Eur J Gastroenterol Hepatol 28(2):210–216, 2016. doi: 10.1097/MEG.0000000000000496