Approximately 50 million individuals have reported symptoms of acne vulgaris, a chronic inflammation of the skin consisting of whiteheads, blackheads, papules, pustules, or nodules. Eighty-five percent of teenagers report having acne, and 12% of adults can continue to have it. Factors causing acne include follicular hyperkeratinization, microbial colonization, sebum production, and inflammatory mechanisms.

The most common bacteria that causes acne is Propionibacterium (P) acnes, a gram-positive anaerobic rod. Most acne isn’t tested for microbes unless conventional treatments are resistant. Androgen levels can also play a role in acne pathogenesis, but most patients have normal hormone levels, so androgen levels play more of a role in treatment rather than diagnosis.

Dietary Considerations
Limited evidence suggests personal diet affects acne severity. Some data suggest patients with high sugar-based diets are more prone to experiencing acne. Studies showed patients with a low glycemic index had less acne as well as a lower BMI, decreased free androgen, and improved insulin sensitivity. Some study results have also shown dairy to increase acne, especially skim milk. Women who report drinking 2 or more glasses of milk per day have an increased risk of acne upwards of 44%.

Topical Treatment
First-line therapy is chosen based on the site and extent. Benzoyl peroxide kills P. acnes and mildly comedolytic ointments prevent the formation of comedones and blemishes. Once the patient begins using benzoyl peroxide, he or she can expect to see results in 5 days and should use lower-strength and water-based formulations if the skin is sensitive.
 
Topical antibiotics available in combination with benzoyl peroxide include clindamycin (preferred) and erythromycin. Azelaic acid and salicylic acid are sometimes used for their comedolytic effects, but azelaic acid can cause lightening of the skin and should be used cautiously with darker skin tones.

Topical retinoids  include tretinoin, adapalene, and tazarotene; being both anti-inflammatory and comedolytic, these are the most effective topical treatments.
 
Retinoids’ adverse effects (AE) include dryness, peeling, erythema, and irritation. If patients have any of these symptoms, they should be advised to decrease the frequency of use. Tretinoin isn’t photo-stable; it must be applied at bedtime and shouldn’t be used with benzoyl peroxide because it can become inactivated. Tazarotene is category X, so all women of childbearing age should be counseled carefully when receiving the prescription. Adapalene 1% gel is approved for patients as young as 9 years, and tretinoin 0.05% micronized is approved for patients 10 years and older. All other retinoid products are approved for patients 12 years or older, limiting their use in early-onset acne.

Antibiotic Treatment
Systemic antibiotics are indicated for moderate to severe acne and should be used in combination with topical retinoids. However, monotherapy of systemic antibiotics isn’t a mainstay therapy because of the resistance developing against antibiotics and the reported correlation between systemic antibiotics and the development of inflammatory bowel disease, pharyngitis, and Clostridium difficile infections. Patients who have started systemic antibiotics should be reevaluated every 3 to 6 months and have their use discontinued as early as possible.

Tetracyclines, a first-line therapy, include doxycycline and minocycline and work by binding to the 30S subunit of the bacterial ribosome; they also have anti-inflammatory effects. Pharmacists can make sure they’re being dosed correctly. Doxycycline is most effective at 1.7 to 2.4 mg/kg and can be dosed once- or twice-daily. It’s important to counsel patients that gastrointestinal (GI) upset, photosensitivity, and dizziness are possible AEs.

Erythromycin and azithromycin are second-line therapies called macrolides. Azithromycin is dosed 3 times per week to 4 times per month to treat acne. Macrolides can cause GI upset and, in severe cases, cardiac conduction abnormalities and even hepatotoxicity.

Bactrim can be effective in treating acne by blocking synthesis of folic acid of the bacteria. However, it’s rarely used because other agents have been proven more effective. Patients should be counseled on GI upset, photosensitivity, and skin AEs including itching, peeling, and development of a rash indicating an allergic reaction. Furthermore, bactrim isn't favored for long-term use due to the rare but potential development of neutropenia, agranulocytosis, anemia, and thrombocytopenia.
Hormonal Therapy
Oral contraceptives (birth control) can also help prevent acne by regulating hormone levels. Four contraceptives are currently approved by the FDA for treatment of acne: ethinyl estradiol/norgestimate, thinyl estradiol/norethindrone acetate/ferrous fumarate, ethinyl estariol/dropirenone, and ethinyl estradiol/drospirenone/levomefolate. These contraceptives decrease androgen production and bind free circulating testosterone to prevent it from activating the androgen receptor, preventing hormone-induced acne.

Pharmacists should counsel all patients that it takes about 3 months of using contraceptives consistently to see a significant improvement in their acne, but when they’re combined with topical treatments, patients may see an improvement in acne symptoms even sooner. Patients should also be counseled on the common AEs, including menstrual irregularities, GI upset, cramping, nausea, vomiting, breast tenderness, and changes in vaginal discharge.

Oral contraceptives manage acne very effectively, but patients should nonetheless weigh the risks and AEs of taking this medication. Long-term severe AEs include blood clots, breast cancer, cervical cancer, low bone mass, and decreased natural production of estrogen.

Spironolactone is also prescribed for acne treatment because it’s a potent aldosterone receptor antagonist, decreasing the binding of testosterone and dihydrotestosterone to androgen receptors on skin cells. Spironolactone is commonly avoided in men due to the development of gynocomastia, but it’s generally well-tolerated and effective in women. Common AEs include increased urination, menstrual irregularities, breast tenderness/enlargement, headache, dizziness, and fatigue. If used concurrently with contraceptives, patients can develop hyperkalemia and should be monitored; however, younger or healthier patients generally don’t have any issues, and the change of hyperkalemia is very low.

Isotretinoin
Isotretinoin is an isomer of retinoic acid and FDA-approved for severe acne resistant to other mainstay treatments. Isotretinoin decreases sebum production, acne lesions, scarring, and even anxiety and depression.

The starting dose is 0.5 mg/kg/day increased to 1 mg/kg/day for maintenance dosing. Some patients can tolerate higher doses, but study results show patients taking the maintenance dose have a significant lower relapse rate and their acne is managed.

Providers and patients must enroll in the iPledge system to prevent pregnancies while prescribing and using this medication due to the teratogenic consequences: isotretinoin is Pregnancy Category X. Along with counseling patients on the AEs of this drug (GI upset, dry/peeling skin, irritability, suicidal thoughts, depression), pharmacists should also advise both men and women to use 2 types of birth control while they or their partners are taking this medication. The 2 most common forms of birth control are oral contraceptives and male condoms.
 
Even though patients enroll in the iPledge system, almost 40% of patients admitted to missing one or more of their contraceptive pills per month while 29% of patients don’t comply with using condoms during sexual intercourse. Approximately 150 patients get pregnant every year while on isotretinoin due to noncompliance, and their offspring have a high rate of congenital malformations, which has been well documented since isotretinoin was introduced in the 1980s.