Acne

Acne vulgaris is one of the most common disorders of the skin in the pediatric population, with an estimated prevalence of 85% in adolescents. Although the severity of acne varies considerably, the majority of patients have mild-to-moderate acne. Acne can cause psychosocial morbidity and have negative effects on quality of life similar to that experienced by people with asthma and epilepsy. Importantly, acne can lead to permanent scarring and disfigurement.

Acne is primarily a disorder of the pilosebaceous unit involving four key factors:

• increased sebum production under the influence of androgens

• alteration in hair follicle growth and differentiation

• inflammation

• bacterial overgrowth (namely Cutibacterium acnes, formerly known as Propionibacterium acnes)

Studies of acne in twins have demonstrated a higher concordance rate among monozygotic than among dizygotic twins, suggesting some genetic influence.

Diagnosis

The diagnosis of acne is clinical and determined by the presence of open and closed comedones (blackheads and whiteheads) and inflammatory lesions (e.g., papules, pustules, and nodules).

Multiple pustules and inflammatory papules on the face (Source: Acne. N Engl J Med 2005.)

Classification of Acne by Age

Pediatric acne can be categorized based on patient age as follows:

Neonatal Acne

Neonatal acne presents in the first several weeks of life with erythematous papules and pustules. It affects up to 20% of neonates and presents more often in males. The cause of neonatal acne is uncertain but is thought by some experts to be mediated by transmission of maternal androgens or endogenous production of hormones by the fetal adrenal glands. However, neonatal acne may be due to an inflammatory reaction to overgrowth or colonization with various forms of yeast of the Malassezia species, suggesting that the term neonatal cephalic pustulosis is more accurate. While most neonatal acne resolves within a few months without treatment, severe (exuberant) cases can be treated with topical medications (e.g., benzoyl peroxide or a topical antibiotic). If yeast is suspected, topical ketoconazole cream may be considered.

Infantile Acne

Infantile acne is distinguished from neonatal acne by the presence of open and closed comedones and onset after 6 weeks of age. Typical presentation is characterized by larger inflammatory papules and pustules on the face. Infantile acne is also more common in males but less common than neonatal acne and has the potential to cause scarring and disfigurement. Complete resolution may take months to years. Recommended treatment, although all off label, includes topical retinoids and antibiotics and occasionally oral antibiotics for resistant acne.

Infantile acne demonstrating papules and pustules on the face. (Source: Wikimedia Commons 2010.)

Mid-Childhood Acne

Mid-childhood acne is considered abnormal and important to recognize because it is believed that typically developing children do not produce significant adrenal or gonadal androgens at this age to develop acne. Referral to a specialist to evaluate for endocrinologic abnormalities is warranted.

Additional signs of androgen excess to look for in patients aged 1-7 years with acne include:

• body odor

• axillary or pubic hair

• hirsutism

• male- or female-pattern hair loss

• truncal obesity

In the absence of hormonal abnormalities, topical therapies are usually effective. Oral antibiotics may be used for moderate-to-severe cases. Note that tetracyclines are not approved by the FDA for use in children younger than 8 years.

Preadolescent and Adolescent Acne

The majority of patients presenting with acne fall in this category. Preadolescent and adolescent acne may be the first sign of puberty and it is characterized by a predominance of comedones on the forehead and central face (the so-called “T-zone”). Many patients ultimately outgrow acne in later adolescence and young adulthood, although a minority of patients may have persistent acne into adulthood.

Acne on the lower face of a young woman. (Source: Acne. N Engl J Med 2005.)

Acne on the face of a 17 year-old male. (Source: Acne. N Engl J Med 2005.)

Classification of Acne Severity

According to the American Academy of Pediatrics (AAP) guidelines, acne may be classified as mild, moderate, or severe based on the number of lesions and amount of skin involved. Additionally, a description of the primary morphology of lesions (e.g., comedonal, inflammatory, cystic/nodular, or mixed) can aid in this classification.

The following images show patients with mild acne with limited papules and pustules and a few closed comedones (top image); moderate inflammatory and comedonal acne with postinflammatory hyperpigmentation noted on the forehead, cheek, and chin (middle image); and severe acne with confluent papules, pustules, and deep nodules (bottom image).

(Source: Acne Vulgaris. N Engl J Med 2018.)

Treatment of Acne

The American Academy of Pediatrics guidelines for the treatment of acne, created by an expert panel of pediatric dermatologists, pediatricians, and adult dermatologists, provide recommendations and evidence-based treatment algorithms. The American Academy of Dermatology also issued more recent guidelines of care for management of acne.

In general, the least aggressive regimen possible should be chosen to minimize adverse effects and increase adherence. Combination therapy is especially important to improve efficacy and decrease the chance of antibiotic resistance. Fixed-dose combination products are available, and, despite their generally higher price, may facilitate adherence to the therapeutic regimen. Topical therapies require at least 6 weeks of use before reassessment for improvement. It is important to provide detailed patient counseling, including expected time to response, before therapy is initiated.

Topical Therapies

Salicylic acid

• Mechanism of action: promotes turnover of the epithelium

• Practical tips: the most common active ingredient in over-the-counter acne preparations; available in many vehicles and concentrations

Benzoyl peroxide

• Mechanism of action: antimicrobial that acts through production of oxygen free radicals and has comedolytic and anti-inflammatory properties

• Practical tips: available as wash, cream, or gel, with or without a prescription

• Recommended for use concurrently with prescribed topical or oral antibiotics to minimize antibiotic resistance

• Can deactivate tretinoin when applied at the same time; washes are preferred for truncal acne to minimize discoloration of clothing

• Adverse effects: higher strengths are associated with more skin irritation; can cause irritant contact dermatitis and rarely allergic contact dermatitis; can bleach clothing and towels

Topical retinoids

• Examples: tretinoin, adapalene, tazarotene, trifarotene

• Mechanism of action: normalizes skin turnover, has comedolytic and anticomedonal properties, and is anti-inflammatory; aids with postinflammatory hyperpigmentation

• Practical tips: titrate to nightly use; use a small amount and apply to the entire face (not just the affected areas); apply in conjunction with a moisturizer

• Adverse effects: irritation, sun sensitivity; tarazotene is teratogenic

Topical antibiotics

• Examples: clindamycin, erythromycin, sulfur, dapsone, minocycline

• Practical tips: use in combination with benzoyl peroxide to minimize bacterial resistance

• Adverse effects: rare reports of topical clindamycin causing Clostridium difficile colitis; odor of sulfur is offensive; sulfur sulfacetamide should be used with caution in patients with drug allergies; dapsone and sulfur can cause yellow-brown discoloration of skin when applied concurrently with benzoyl peroxide

Azelaic acid

• Mechanism of action: naturally occurring dicarboxylic acid; antibacterial and anticomedonal effects

• Practical tip: aids with postinflammatory hyperpigmentation; safe for use during pregnancy

• Adverse effects: burning, tingling, itching at application site

Topical clascoterone

• Mechanism of action: androgen receptor inhibitor at the site of application

• Practical tip: only hormonal treatment that can be used in both males and females >12 years of age

• Adverse effects: erythema, dryness, rarely striae, nasopharyngitis, headache

Oral Therapies

Oral antibiotics

• Examples: sarecycline, minocycline, doxycycline

• Mechanism of action: decrease bacterial load, free fatty acids in sebum, and inflammation

• Practical tips: plan shortest course possible, no more than 3 to 4 months to minimize development of bacterial resistance

• Adverse effects: antibiotic resistance; tooth discoloration in children younger than 8 years; pill esophagitis with doxycycline; photosensitivity and gastrointestinal upset with tetracycline and doxycycline; pigmentation of the skin, nails, and mucous membranes; severe drug-induced hypersensitivity with minocycline; sarecycline is associated with the least phototoxic and gastrointestinal reactions

Combined oral contraceptives

• FDA-approved for acne vulgaris:

  • ethinyl estradiol-norgestimate

  • ethinyl estradiol-norethindrone

  • ethinyl estradiol-drospirenone

• When considering oral contraceptives in patients with acne, progestins with lower androgen activity are considered more desirable. Although norethrindrone-containing oral contraceptives are FDA approved for acne, third- and fourth-generation progestins (e.g., desogestrel, norgestimate, and drospirenone) are preferred because they are less androgenic or antiandrogenic.

• Practical tip: most helpful in patients with hormonal acne flares associated with menstruation or distributed on the cheeks, jawline, and chin

• Adverse effects: venous thromboembolism, myocardial infarction, stroke

• Contraindications: migraine with aura, history of venous thromboembolism or stroke, factor V Leiden deficiency

Spironolactone (oral form)

• Off-label use for hormonal acne

• Mechanism of action: competes for androgen receptors on target cells; potassium-sparing diuretic

• Adverse effects: menstrual irregularities, breast tenderness, hyperkalemia, fatigue

• Practical tips: safe for most patients without medical comorbidities; routine lab monitoring for potassium levels is not recommended for otherwise healthy females younger than 45 years

• Black-box warning: shown to be tumorigenic in chronic toxicity studies in rats, resulting in the growth of benign endocrine tumors, but has not been associated with increased risk of tumors in humans

Isotretinoin (Accutane)

• Mechanism of action: oral retinoid; works against all four pathogenetic factors by decreasing sebum, bacterial concentration, and inflammation, with strong comedolytic effects

• Traditional dose: cumulative goal dose of 120-150 mg/kg in the course of treatment (usually approaching 6 months)

• Practical tips: regulated by the FDA-mandated monitoring program iPLEDGE due to teratogenic effects, requires persons of child-bearing potential to use two forms of contraception or abstinence during treatment and take monthly pregnancy tests

  • monitor triglycerides and alanine transaminase at baseline and at peak dose

  • targeting a higher cumulative goal and continuing treatment for longer duration after acne clearance (at least 2 months) is important to prevent relapse

• Adverse effects:

  • teratogenic

  • common cutaneous adverse effects include skin dryness, cheilitis

  • associations with depression and suicide as well as inflammatory bowel disease are described but not causally proven

  • risk of acne fulminans if dosed too high

  • see the AAD position statement regarding the use of isotretinoin

Diet and Acne

The AAD guidelines for the management of acne address the role of diet and acne with the following:

• No specific dietary changes are recommended.

• Emerging data suggest that high-glycemic-index diets and Western diets may be associated with acne.

• Limited evidence suggests that dairy products worsen acne.

Drug-Induced Acne

Medications that can trigger or worsen acne include the following:

• phenytoin

• isoniazid

• progestin

• lithium

• epidermal growth factor receptor (EGFR) inhibitors

• glucocorticoids

• janus kinase (JAK) inhibitors

Supplements that can worsen or trigger acne include the following:

• whey protein

• creatine

Hormonal Acne

Acne in males and females can be caused or exacerbated by androgen excess. Adolescent females are the most likely pediatric patients to be affected by androgen-related exacerbation.

Features of hormonal acne may include:

• lack of response to traditional therapies

• located on the cheeks, chin, jawline

• flares with menstruation

• association with other signs of androgen excess

A workup for polycystic ovarian syndrome (PCOS) or other endocrine abnormalities should be considered in patients with other signs of androgen excess. Treatments for hormonal acne include combined oral contraceptives and spironolactone.

Acne Fulminans

Acne fulminans is a rare, severe form of acne vulgaris that presents with painful, nodular, and/or ulcerative lesions, and occasionally fever and musculoskeletal pain. It is more common in males and can be triggered by initiation of therapy with isotretinoin. Acne fulminans is generally treated with systemic glucocorticoids concurrently with lower doses of isotretinoin.

Periorificial Dermatitis

Periorificial dermatitis is in the differential diagnosis of acne vulgaris. It presents with small, pink or skin-colored papules surrounding the mouth, nose, and eyes and/or with diffuse central facial erythema. Periorificial dermatitis is often triggered or exacerbated by topical steroids and inhaled glucocorticoids used to treat asthma. Other triggers include fluorinated toothpaste. Topical or oral antibiotics can be used for treatment.