Acne Vulgaris

 Acne Vulgaris:

INTRODUCTION:

Acne vulgaris affects up to 95 percent of teenagers and young adults but can begin in infancy and early childhood. This topic will discuss the pathogenesis, diagnosis, and management of acne in infants and children younger than 12 years. Neonatal acne, a common acneiform eruption occurring in the first months of life, is discussed elsewhere. Acne in adolescents and adults is also discussed separately.

CLASSIFICATION:

Acne in childhood is divided into three groups, based on age at presentation, differences in clinical presentations, associated conditions, and pathogenetic factors:

●Infantile acne – Infantile acne typically occurs at the age of 6 to 16 months (median 9 months) and lasts for up to two years. It is most often due to temporary, physiologic imbalances in androgen production.

●Mid-childhood acne – Mid-childhood acne has onset between one to seven years of age, a time when androgen levels should be at their nadir. Acne in this age group may reflect an increased androgen production, most often due to premature adrenarche.

●Preadolescent acne – Preadolescent acne is defined as acne occurring with the early rise in adrenal androgens between 7 to 12 years, heralding the start of puberty.

EPIDEMIOLOGY:

Acne in children and preadolescents is uncommon. In an analysis of the National Ambulatory Medical Care Survey looking at all physician office visits for acne (1993 through 2009), 4.8 percent were for preadolescent acne, 0.9 percent were for mid-childhood acne, and 3 percent were for neonatal or infantile acne. Approximately 91 percent of visits were for adolescent acne.

Infantile acne occurs more frequently in males than in females, while mid-childhood acne affects females more commonly than males.

PATHOGENESIS:

Infants often have physiologic, transient increased levels of adrenal androgens. At birth, the immature adrenal gland can produce elevated levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which typically normalize by six months of age [6]. In babies with acne, these adrenal androgen elevations may be prolonged. Additionally, in infants 6 to 12 months of age, there is an increased production of luteinizing hormone at pubertal levels ("mini-puberty"), which in male infants results in additional production of gonadal testosterone, further contributing to acnegenesis. These hormonal imbalances are typically transient, and acne will improve as the hormone levels normalize. Genetic factors likely influence acnegenesis as well, as approximately 50 percent of babies with infantile acne have a sibling with infantile acne and a positive family history of severe, adolescent acne.

Mid-childhood acne is, in most cases, associated with increased androgen production due to premature adrenarche or, more rarely, to other disorders associated with hyperandrogenism, such as nonclassic (late-onset) congenital adrenal hyperplasia, gonadal or adrenal tumors, or conditions associated with precocious puberty. Premature adrenarche (often presenting with early acne) has been associated with low birth weight, due to hormonal stressors, and potential increased risk for polycystic ovarian syndrome (PCOS) and metabolic syndrome. Exogenous exposure to testosterone gel and other androgens has also resulted in virilization with associated acne.

CLINICAL MANIFESTATIONS:

The clinical manifestations of acne in children vary depending on age.

Infantile acne — Infantile acne typically occurs at the age of 6 to 16 months (median 9 months) with typical acne lesions distributed over the cheeks. Mixed, inflammatory papules and pustules and comedones are common, with nodular lesions being infrequently seen in this age group. In most cases, babies with infantile acne do not have other signs or symptoms of hyperandrogenism. The eruption is usually self-limited and generally resolves spontaneously by the end of the first year of life but may persist until two years of age. Scarring, presenting as typically small, atrophic pits, may result in up to 50 percent of affected infants.

Mid-childhood acne — Mid-childhood acne presents in children of one to seven years of age with comedones and inflammatory lesions typically distributed over the forehead, cheeks, and nose. Because children aged one to seven years do not produce significant amounts of androgens, acne in this age group suggests an endocrine abnormality that warrants evaluation by a pediatric endocrinologist.

Preadolescent acne — Preadolescent acne usually presents in children aged 7 to 12 years, predominantly with mild to moderate numbers of comedones in the T-zone (ie, forehead, nose, and chin and, less frequently, with papules, pustules, and nodules.

DIAGNOSIS:

History – Relevant history includes age of onset; history of acne in parents and siblings; and medical and medication history, including use of oral, inhaled, or topical corticosteroids and other agents that may elicit acneiform drug eruptions (eg, cyclosporine, chemotherapy agents). Accidental exposure to exogenous androgens (eg, androgen-containing topical preparations or supplements used by parents or caregivers) should also be investigated.

●Physical examination – All children with acne should undergo a comprehensive physical examination for signs of androgen excess and advanced Tanner stage.

Children with premature adrenarche and subsequent pubarche will exhibit pubic hair and adult-type body odor without other signs of secondary sex development. The presence of additional secondary sexual characteristics, such as breast development, testicular enlargement, atypical genitalia, accelerated growth, and muscular habitus, raise suspicion of disorders associated with precocious puberty or other causes of hyperandrogenism, such as nonclassic (late-onset) congenital adrenal hyperplasia, androgen-secreting tumors, or exposure to exogenous androgens.

Skin biopsy and histopathology — Histopathology is rarely required to make a diagnosis of acne. In atypical cases where the diagnosis is unclear, a small 2 to 3 mm punch biopsy of a characteristic lesion in the least aesthetically sensitive area (away from the central face and cheeks) is recommended.

On histopathology, comedones will demonstrate an open or closed, follicular orifice with a keratinaceous plug and mild, perifollicular inflammation. With follicle wall rupture, bacteria and mixed inflammation (neutrophils, lymphocytes, histiocytes) surround the pilosebaceous unit. Foreign body type multinuclear giant cells and granulomatous inflammation may be seen. Fibrosis and scarring are seen in later lesions.

Assessment of severity — Standardized acne assessments for childhood acne have not been established. The following five-point Investigator's Global Assessment (IGA) scale (used in a clinical trial for preadolescent acne can be used:

●Clear (0) – No comedones. Papules or pustules, residual hyperpigmentation, and erythema may be present.

●Almost clear (1) – Rare comedones. No more than a few small papules and pustules.

●Mild (2) – Easily recognizable comedones in limited numbers, with or without the presence of small papules and pustules.

●Moderate (3) – Many comedones with or without easily recognizable, small and medium-sized papules. No nodules or cysts.

●Severe (4) – Widespread and numerous comedones. Many small, medium-sized, and large papules and pustules; nodules or cysts may or may not be present.

TREATMENT:

Mild acne — Monotherapy with topical tretinoin 0.025% cream or adapalene 0.1% gel or combination therapy with benzoyl peroxide 2.5% gel plus tretinoin 0.025% cream or adapalene 0.1% gel can be used for mild acne in preadolescents. Simplifying routines in this age group is especially important to encourage better adherence. For combination therapy, once-daily routines (eg, benzoyl peroxide wash with adapalene 0.1% gel) or fixed combination products (eg, adapalene-benzoyl peroxide 0.1%/2.5% gel) may ease compliance.

Topical dapsone is a second-line topical treatment for mild, inflammatory acne for children ≥9 years [40]. Dapsone gel 7.5% is applied once daily. Dapsone should not be applied at the same time as benzoyl peroxide, as they can cause a temporary orange discoloration of skin and hair.

Topical therapies for preadolescent acne have been evaluated in several randomized trials:

●Adapalene-benzoyl peroxide – In a randomized trial that included 285 children aged 9 to 11 years with moderate acne treated with adapalene-benzoyl peroxide 0.1%/2.5% gel or vehicle, the percent reduction in lesion count at 12 weeks was greater in the active treatment group than in the vehicle group (69 versus 19 percent).

●Tretinoin – In a randomized trial with 110 children aged 9 to 11 years, treatment with topical tretinoin 0.04% microsphere gel (55 patients) induced a statistically significant greater mean reduction in noninflammatory lesions compared with vehicle (-19.9 versus -9.7, respectively) at 12 weeks.

A post-hoc analysis of two multicenter, phase 3, randomized trials of tretinoin 0.05% lotion versus vehicle in 154 children aged 9 to 13 years with moderate to severe acne found a mean percent reduction in inflammatory and noninflammatory lesion counts of 50 and 44 percent, respectively, in the tretinoin group compared with 31 and 19 percent, respectively, in the vehicle group at 12 weeks.

●Topical dapsone – Dapsone 7.5% gel was evaluated in a phase 4, open-label, multicenter study in 100 patients 9 to 11 years of age. At 12 weeks of treatment, total lesion counts decreased by 24, with a mean percentage reduction of 51.9 percent.

Moderate to severe acne — Oral antibiotics, while maintaining topical treatments, are the first-line therapy for preadolescents with moderate to severe acne. Doxycycline is approved for children ≥8 years of age and should not be used in younger children due to the potential for yellow staining of teeth.

For children ≥8 years of age, the recommended dose of doxycycline is 50 to 100 mg once or twice daily or 150 mg once daily.For children unable to swallow pills, doxycycline is commercially available in liquid suspension 25 mg/5 mL or syrup 50 mg/5 mL. Doxycycline may be given with food to minimize gastrointestinal upset.

Erythromycin (10 mg/kg/dose, one to two times daily) or azithromycin (5 mg/kg once daily, maximum daily dose 250 mg) are alternative antibiotics for children <8 years of age.

Systemic antibiotic therapy should be limited to three months and then discontinued, while topical therapy with a retinoid with or without benzoyl peroxide is maintained.

Severe acne — For severe, nodular acne and acne not responsive to systemic antibiotics, isotretinoin may be used. Dosing is the same as for adolescent acne (0.5 to 1 mg/kg/day for 20 weeks), with a cumulative dose of 120 to 150 mg/kg.