The Pathophysiology of Acne Vulgaris in Children and Adolescents, Part 1
Microcomedones, the earliest lesions of acne, appear at adrenarche, which typically occurs at about 8 years of age when androgens of adrenal origin begin to stimulate follicular hyperkeratosis and sebaceous hyperplasia in pilosebaceous units on the face. Comedones appear about 2 years later, when androgens of gonadal origin are produced and colonization of follicles by Propionibacterium acnes increases. Inflammatory lesions, such as pustules, papules, and nodules, are the result of the host's immune responses to P acnes; the proinflammatory cytokines are released by immunocompetent leukocytes that are recruited in response to this bacterium and its metabolic by-products. Androgens also affect the barrier function of the skin, and disturbances of barrier function may stimulate epidermal DNA synthesis. This leads to epidermal hyperplasia, which may also contribute to follicular hyperkeratosis in acne. Optimal treatment for this disorder will address these various pathophysiologic factors.
The clinical implications of these findings are unclear because skin diseases that may be associated with compromised barrier homeostasis appear to be as common in women as men. However, gender may influence the severity rather than the prevalence of some dermatologic disorders, such as acne, through its impact on barrier function. For example, it has been postulated that follicular hyperkeratosis in acne may result from a linoleic acid deficiency in the follicular epithelium36 and that retention of desquamated cornified cells in the follicular canal is caused by an imbalance of free sterol and cholesterol sulfate in comedonal lipids.37 In addition, acute or chronic disturbances of barrier function may stimulate epidermal DNA synthesis, leading to epidermal hyperplasia, which also might contribute to follicular hyperkeratosis in acne.32
Yamamoto and coworkers38 examined the role of the sebum secretion rate and the lipid content and barrier function of the stratum corneum in 36 patients with acne and 29 controls. The sebum secretion rate over 3 hours was significantly greater in patients with moderate acne, but not mild acne, compared with controls. Sphingolipids (ceramides and free sphingosine) in the stratum corneum were significantly different among patients with moderate acne, mild acne, and controls, with the lowest concentrations in patients with moderate acne. Similarly, barrier function was reduced to the greatest extent in patients with moderate acne, with lower levels of sphingolipids corresponding to diminished barrier function. These results suggest that an impaired barrier function caused by decreased amounts of ceramides may be responsible for the formation of comedones because barrier dysfunction is accompanied by hyperkeratosis of the follicular epithelium.38
Conclusion
Acne is a disorder of childhood and adolescence, and increasing levels of circulating androgens of adrenal and gonadal origin seem to trigger the condition. The pathophysiology of acne includes, in a somewhat sequential manner, retention hyperkeratosis, sebaceous gland hyperplasia and increased sebum production, colonization of the follicles by P acnes, and perifollicular inflammation. The goals of therapy are to reverse these pathogenetic events and thereby minimize or prevent acne lesions.
Part 2 of this article will discuss treatment options for children and adolescents based on the pathophysiology of acne.
