Acne is predominantly a disorder of late childhood and adolescence, despite the fact that it may persist into, recur, or begin during adulthood. Although acne has been reported in otherwise healthy children as young as 8 years,1 and even earlier in those with abnormal virilization or precocious puberty,2 most cases occur between the ages of 14 and 19 years.1 The prevalence of acne was assessed among 6768 boys and girls aged 12 to 17 years in the National Health Examination Survey of 1966 to 1970.3 Based on physical examinations, only an estimated 27.7% of children were found to have essentially normal skin, whereas 68.1% had lesions diagnosed as facial acne (minimal requirement for diagnosis was sparse comedones with no inflammatory reaction). Prevalence increased with age more rapidly among younger than older youths, from 39% at age 12 years to 86.4% at age 17 years, and the increase in prevalence with age was more rapid and consistent among boys than girls. Although facial acne was about as prevalent among girls as boys in the 12- to 17-year age range (69.8% and 66.4%, respectively), the onset occurred somewhat earlier in girls, and the severity tended to be greater in boys. More severe facial acne (defined in the survey as at least comedones, small pustules, and a tendency toward inflamed lesions deeper than the follicular orifice) was present in a much smaller proportion of youths.
More recently, estimates from the National Health Interview Survey of 1996, which included 24,371 households containing 63,402 persons, identified "chronic" acne (acne with a duration >3 months) in 2.44% of those 17 years and younger,4 which corresponds approximately with the prevalence of "more severe facial acne" in the earlier survey. These results suggest a relationship between the onset of puberty and the pathophysiology of acne. This article reviews recent advances in our understanding of acne in children and adolescents, with an emphasis on the triggering role of adrenarche. Part 2 of this article will review treatment options.
Pathophysiology of Acne
A number of pathophysiologic factors contribute to the development of acne, beginning with increased prepubertal androgen production, followed in a generally sequential manner by abnormal pilosebaceous follicular keratinization and desquamation; increased proliferation of sebocytes, enlarged sebaceous glands, and augmented secretion of sebum; obstruction of sebaceous follicles; colonization of pilosebaceous units by Propionibacterium acnes; and perifollicular inflammation.5-13 Follicular hyperkeratinization, sebocytic hyperplasia, and seborrhea are all dependent on androgens.14-16
Role of Adrenarche
The pathogenetic process appears to commence with androgenic hormonal stimulation of pilosebaceous units, the density of which is greatest on the face and scalp (400–800 glands/cm2) and least on the extremities (50 glands/cm2).5 Before levels of circulating androgens increase, pilosebaceous units consist of soft, fine, unpigmented vellus hairs and small sebaceous glands.17 Circulating androgens bind to androgen receptors that are localized to the basal layer of the outer-root–sheath keratinocytes of the hair follicle and to sebaceous glands.15 In sexual hair areas, such as the axilla, pilosebaceous units begin to differentiate into large terminal hair follicles. In sebaceous areas, such as the face, pilosebaceous units become sebaceous follicles while the hair remains vellus.17 Without a source of circulating androgens, the sebaceous glands remain small.6
The adrenals and the gonads produce the majority of circulating androgens.15 During the prepubertal period, adrenal androgens appear to be the major determinant of sebaceous gland activity.18 In both boys and girls, plasma concentrations of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) normally begin to increase at adrenarche, or adrenal puberty, which typically occurs at about age 8 years, and continue to rise through puberty.19 Conditions such as adrenal hyperplasia or polycystic ovary disease are associated with hyperandrogenism; sudden onset of acne or treatment-resistant acne may be associated with these conditions.15
Androgen stimulation drives the changes in both follicular keratinocytes and sebocytes that lead to the formation of microcomedones,10 which are not visible but are already present in 40% of children aged 8 to 10 years.17 Microcomedones develop when desquamated cornified cells of the upper canal of the sebaceous follicle become highly adherent and obstruct the lumen in the presence of increased sebum production (retention hyperkeratosis).
The onset of adrenal production of DHEA and DHEAS is followed by a rise in plasma levels of adrenal androstenedione 1 to 2 years later, which approximately coincides with an increase in gonadal testosterone production—the so-called gonadarche or pubarche. It is at this time that microcomedones begin to enlarge and become visible, forming open and closed comedones, which are noninflammatory lesions.10 This comedogenesis may be driven in part by increased levels of interleukin 1α, which is derived from ductal keratinocytes.20 Colonization of the follicular canal with P acnes, an anaerobic, aerotolerant, lipophilic diphtheroid that thrives in triglyceride-rich sebum, follows comedogenesis.21 Inflammatory acne appears to be the result of the host response to P acnes and the proinflammatory cytokines released by immunocompetent cells that are recruited by this bacterium and its metabolic by-products.11,13,21,22 Depending on the intensity of the inflammatory process and its localization within the follicle, erythema, superficial pustules, papules, and/or nodules (cysts) may develop.7 Most patients have a variety of noninflammatory and inflammatory lesions, though some have predominantly one type or the other.8 It is currently believed that hypersensitivity to P acnes determines the magnitude of the immunologic response and, accordingly, the severity of inflammatory acne in individual patients.23