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Acne: Step Up the Use of Nonantibiotic Systemic Therapy.

Despite acne's high prevalence (~50 million people in the United States (1)), its physical and psychological morbidity during adolescence, and association with lifelong scarring, dermatologists do not always treat it aggressively. The treatment goal should be to have clear or almost clear skin, although not every patient will reach that goal. Greater use of combination oral contraceptives (COCs), spironolactone, and oral isotretinoin in appropriate patients can improve outcomes, reduce the use and duration of oral antibiotics, and lower the risk of inducing antibiotic resistance, in line with the American Academy of Dermatology (AAD) guidelines. (1)

Off-label use of spironolactone for acne in adolescents and adults ages 12 to 40 years increased substantially from 2004 through 2013, based on a retrospective claims data analysis. Use of oral contraceptives (OCs), isotretinoin, and antibiotics did not change substantially during this time period, however. (2) Mean duration of oral antibiotic therapy was about 6 months, double the duration recommended in the AAD guidelines. (1,2)

Research results discussed below debunk some misconceptions about nonantibiotic systemic agents that may limit their use.

Combination Oral Contraceptives: Risks vs Benefits

Risk of Venous Thromboembolism (VTE)

COCs roughly double the risk of VTE in women of reproductive age compared with non-users of the same age range, from 4 to 5 per 10,000 women per year to 8 to 9 per 10,000 women per year. But these risks are still much lower than the VTE risk associated with a third-trimester pregnancy and puerperium (Figure). (3) Therefore, preventing pregnancy in sexually active women reduces the risk of VTE more than COCs raise the risk of VTE. The risk-benefit balance is different in someone who is not sexually active.

Effect on Risk of Cancers

COCs have been shown to reduce the risk of colorectal, endometrial, and ovarian cancer, while increasing the risk of cervical and breast cancer. (4,5)

Interactions With Antibiotics

Rifampin and griseofulvin are the only anti-infectives documented to interact with COCs and reduce their effectiveness. (1,6,7)

Contraindications

COCs should be avoided for treating acne in patients during pregnancy or less than 6 weeks postpartum. Other contraindications and cautions include smoking, migraines, hypertension, and breast cancer. (8) The risk-benefit ratio may be different for patients seeking acne treatment rather than contraception and should be considered for each individual.

Spironolactone

No Potassium Monitoring Needed in Most Patients With Acne

A retrospective data analysis reported that the rate of hyperkalemia in women (18-45 years old, no cardiovascular disease or renal failure) receiving spironolactone for acne (n=974) was similar to the baseline rate in healthy young women not taking this medication (n=1165). The study authors concluded that potassium monitoring is unnecessary in otherwise healthy young women taking spironolactone for acne. (9)

The A AD guidelines advise considering monitoring potassium at baseline, during therapy, and after dose increases in older patients and in patients who are also taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, or digoxin. (1)

Spironolactone is not linked to breast cancer in humans, based on 2 large registry studies (2.3 million women age [greater than or equal to]20 years; ~1.3 million women age >55 years). (10,11)

Pregnancy and Nursing

Spironolactone should not be used during pregnancy, but it is compatible, although rarely used, with breastfeeding. (12)

Isotretinoin

Measure Lipid and Hepatic Panels at Baseline and at 8 Weeks, in the Absence of Abnormalities or Medical History Suggesting the Need for More Frequent Monitoring or Dosing Changes

A 26-study meta-analysis found that the mean changes in laboratory values during isotretinoin therapy did not cross into high-risk levels. Additionally, the proportion of patients with laboratory abnormalities was low. (13) The main concerns are liver function test results and triglyceride levels. Acute pancreatitis associated with elevated triglyceride concentrations generally occurs at levels higher than 1000 mg/dL. (14) To reduce the overall risk, keep triglycerides below 500 mg/dL through lifestyle interventions and isotretinoin dose reduction. If necessary, a triglyceride-lowering agent, such as fenofibrate, can be prescribed.

Isotretinoin Is Not Associated With an Increased Risk of Ulcerative Colitis

A French study of 50 million individuals found no association between isotretinoin and ulcerative colitis but did find a link to a decreased risk of Crohn's disease. (15)

Treatment with mechanical dermabrasion or fully ablative lasers should be delayed in patients being treated with isotretinoin. (16)

Summary

The goal of acne therapy should be achievement of clear or almost clear skin. COCs, spironolactone, and isotretinoin, when used in appropriate patients, are alternatives that minimize the use and duration of systemic antibiotics for acne, as recommended by AAD guidelines. (1)

A Topical Therapy for Acne Scars

Scarring is a lifelong reminder of acne for many patients. Treatment for atrophic scars typically involves invasive procedures such as chemical peels, dermabrasion, laser resurfacing, needling, radiofrequency, stem cell therapy, and volumizing fillers. (17) Cost and some patients' desire to avoid invasive measures limit the utility of these options.

The topical retinoid adapalene 0.3% gel alleviated scarring in patients with moderate or severe atrophic acne scars but no active disease. (18) Patients in this recent study applied adapalene 0.3% gel once daily for 4 weeks, then twice daily for another 20 weeks. More than half of the patients completing 6 months of therapy (10/18; 55 6%) demonstrated a 1- or 2-grade improvement from baseline in the full-face global scarring grade. Half the patients demonstrated a 1- or 2-grade improvement after treatment cessation (weeks 48-72). No treatment-related adverse events were reported. Most (88%) patients were satisfied with the gel's effectiveness. (18)

Other studies show that adapalene 0.1% or 0.3% combined with benzoyl peroxide 2.5% reduced scar formation and scar severity compared with vehicle during 6 months of therapy in patients with active inflammatory acne and scarring. (19,20)

References

(1.) Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33.

(2.) Barbieri JS. James WD, Margolis DJ. Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: a retrospective analysis, 2004-2013. J Am Acad Dermatol. 2017;77(3):456-463.e4.

(3.) Reid RL Oral contraceptives and venous thromboembolism: pill scares and public health. J Obstet Gynaecol Can. 2011:33(11): 1150-1155.

(4.) Gierisch JM, Coeytaux RR, Urrutia RP, et al. Oral contraceptive use and risk of breast, cervical colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev. 2013;22(11): 1931-1943.

(5.) Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371(9609):303-314.

(6.) Archer JS, Archer DF. Oral contraceptive efficacy and antibiotic interaction: a myth debunked. J Am Acad Dermatol. 2002;46(6):917-923.

(7.) ACOG Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 73: Use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol. 2006: 107(6): 1453-1472.

(8.) Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016;65(3):1-103.

(9.) Plovanich M, Weng QY, Mostaghimi A. Low usefulness of potassium monitoring among healthy young women taking spironolactone for acne. JAMA Dermatol. 2015;151(9):941-944.

(10.) Biggar RJ, Andersen EW. Wohlfahrt J, Melbye M. Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol. 2013;37(6):870-875.

(11.) Mackenzie IS, Macdonald TM, Thompson A, Morant S, Wei L. Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ. 2012:345:e4447.

(12.) Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: part I. Pregnancy. J Am Acad Dermatol 2014;70(3):401.e1-14.

(13.) Lee YH, Scharnitz TP, Muscat J, Chen A, Gupta-Elera G, Kirby JS. Laboratory monitoring during isotretinoin therapy for acne: a systematic review and meta-analysis. JAMA Dermatol. 2016;152(1):35-44.

(14.) Karalis DG. A review of clinical practice guidelines for the management of hypertriglyceridemia: a focus on high dose omega-3 fatty acids. Adv Titer. 2017;34(2):300-323.

(15.) Racine A, Cuerq A, Bijon A, et al. Isotretinoin and risk of inflammatory bowel disease: a French nationwide study. Am J Gastroenterol. 2014;109(4):563-569.

(16.) Spring LK, Krakowski AC, Alam M, et al. Isotretinoin and timing of procedural interventions: a systematic review with consensus recommendations. JAMA Dermatol 2017;153(8):802-809.

(17.) Zaleski-Larsen LA, Fabi SG, McGraw T, Taylor M. Acne scar treatment: a multimodality approach tailored to scar type. Dermatol Surg. 2016;42(suppl 2):S139-149.

(18.) Loss MJ, Leung S, Chien A. Kerrouche N, Fischer AH, Kang S. Adapalene 0.3% gel shows efficacy for the treatment of atrophic acne scars. Dermatol Ther (Heidelb). 2018;8(2):245-257.

(19.) Dreno B. Bissonnette R, Gagne-Henley A. et al. Prevention and reduction of atrophic acne scars with adapalene 0.3%benzoyl peroxide 2.5% gel in subjects with moderate or severe facial acne: results of a 6-month randomized, vehicle-controlled trial using intra-individual comparison. Am J Clin Dermatol 2018:19(2):275-286.

(20.) Dreno B, Tan J, Rivier M. Martel P, Bissonnette R. Adapalene 0.1%/benzoyl peroxide 2.5% gel reduces the risk of atrophic scar formation in moderate inflammatory acne: a split-face randomized controlled trial. J Eur Acad Dermatol Venereol. 2017;31(4):737-742.
FIGURE. Approximate Risk of Venous Thromboembolism in
  Healthy Women of Reproductive Age per 10,000

Baseline risks               4

Risk with combination
oral contraceptives          6

Risk with a contraceptive
containing drospirenone      9

Risk during pregnancy       12

Risk during puerperium      30

Source: Reid RL.J Obstet Gynaecol Can. 2011;33:1150-115. (3)
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Author:Gold, Linda F. Stein
Publication:Dermatology News
Date:Aug 1, 2019
Words:1633
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