Acne Vulgaris

Etiology references

1. 1. Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in teenaged boys. J Am Acad Dermatol. 2008;58(5):787-793. 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. 2007;57(2):247-256. 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. 2008;159(4):990-991. 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. 2016;152(4):399-404. doi: 10.1001/jamadermatol.2015.4499

Diagnosis references

1. 1. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30. doi:10.1016/j.jaad.2023.12.017

2. 2. Bae IH, Kwak JH, Na CH, et al. A Comprehensive Review of the Acne Grading Scale in 2023. Ann Dermatol. 2024;36(2):65-73. doi: 10.5021/ad.23.094

Mild acne

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 with topical retinoids (eg, tretinoin) may be sufficient for the treatment of mild acne that is exclusively comedonal. 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, trifarotene, and tazarotene are retinoids; like tretinoin, they are usually somewhat irritating and photosensitizing. Azelaic acid has comedolytic and antibacterial properties via an unrelated mechanism and may be synergistic with retinoids.

Combination therapy (eg, a combination of tretinoin with benzoyl peroxide, a topical antibiotic, or both) should be used to treat mild papulopustular (inflammatory) acne. Typical topical antibiotics used include erythromycin and 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). A combination of clindamycin phosphate, adapalene, and benzoyl peroxide is available in the United States.

Physical extraction of comedones using a comedone extractor is an option for patients unresponsive to topical treatment. Comedone extraction may be performed 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, tetracyclines) are generally reserved for moderate and severe acne, but may be used when wide distribution of lesions makes topical therapy impractical, or if there is clinical concern for worsening or progression.

Clascoterone is a 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 erythema, scaling or dryness, and pruritus; although hyperkalemia and hypothalamic-pituitary-adrenal axis suppression have been predicted based on its mechanism, these effects have not been noticed clinically (7).

Moderate acne

Oral systemic therapy with antibiotics is typically included in the treatment of moderate acne (1). Antibiotics effective for acne include tetracyclines (eg, tetracycline, minocycline, doxycycline, sarecycline), and macrolides (eg, erythromycin, azithromycin). Full benefit takes ≥ 12 weeks. Systemic antibiotic use should be limited when possible, to reduce the risks of resistance and other antibiotic-related complications.

Topical therapy, as for mild acne, is usually used concomitantly with oral antibiotics. Topical agents may less commonly be used independently, such as when oral agents are discontinued but treatment must be continued.

Doxycycline and minocycline are preferred antibiotic 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. The dosage of doxycycline and minocycline 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 (dosing is weight-based at 1.5 mg/kg; typical doses range from 60 mg to 150 mg orally once a day) (1). Antibiotics may be discontinued if topical therapy maintains control.

Macrolides (erythromycin and azithromycin) are alternative antibiotics, but they are more likely to cause gastrointestinal adverse effects and antibiotic resistance. Some clinicians also use trimethoprim/sulfamethoxazole (TMP-SMX), also called cotrimoxazole. However, antibacterial resistance may develop, and TMP-SMX 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.

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

Severe acne

Oral isotretinoin is typically reserved for the treatment of patients with moderate acne in whom other oral and topical therapies have been unsuccessful and for those with severe inflammatory acne (1). Dosage of isotretinoin is usually 1 mg/kg in total once a day for 16 to 20 weeks; the total dose may also be administered divided equally twice a day. If adverse effects make this dosage intolerable (see Medications Used to Treat Acne), 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 2 or more 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 remarkably effective in practice; however, the quality of evidence to support its use is low (1, 9). Its use is also 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 has been much publicized but has not been supported by population-level evidence, and treatment may actually improve psychiatric outcomes (10). However, rare mood reactions can occur, particularly in adolescents and those with a pre-existing history of psychiatric disorders, and close monitoring is warranted. Although the 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 (11).

Baseline complete blood count, liver tests, triglyceride, and cholesterol levels should be obtained before treatment. Each should be reassessed at 4 to 8 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 must be 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. Tests excluding pregnancy should be performed before beginning therapy and monthly until 1 month after therapy stops.

Cystic acne

Intralesional glucocorticoid injections (eg, 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.

Other forms of acne

Pyoderma faciale is treated with oral glucocorticoids and isotretinoin.

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

Acne conglobata is treated with oral isotretinoin and systemic glucocorticoids 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.

Scarring

Small scars can be treated with chemical peels, laser resurfacing, microneedling, 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.

Treatment references

1. 1. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30. doi:10.1016/j.jaad.2023.12.017

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. 2017;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. 2020;34(9):2106-2110. doi: 10.1111/jdv.16302

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

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

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. 2020;156(6):621–630. 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. 2013;149(12):1392–1398. doi: 10.1001/jamadermatol.2013.6746

9. 9. Costa CS, Bagatin E, Martimbianco ALC, et al. Oral isotretinoin for acne. Cochrane Database Syst Rev. 2018;11(11):CD009435. Published 2018 Nov 24. doi:10.1002/14651858.CD009435.pub2

10. 10. Tan NKW, Tang A, MacAlevey NCYL, et al. Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis. JAMA Dermatol. 2024;160(1):54-62. doi:10.1001/jamadermatol.2023.4579

11. 11. 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. 2016;28(2):210–216. doi: 10.1097/MEG.0000000000000496

Prognosis reference

1. 1. Collier CN, Harper JC, Cafardi JA, et al: The prevalence of acne in adults 20 years and older. J Am Acad Dermatol 58(1):56-59, 2008. doi: 10.1016/j.jaad.2007.06.045