Article

The Pathophysiology of Acne Vulgaris in Children and Adolescents, Part 1

Cutis. 2004 August;74(2):92-97

References

Ebling FJ, Cunliffe WJ. Disorders of the sebaceous glands. In: Champion RH, Burton JL, Ebling FJ, eds. Textbook of Dermatology. 5th ed. Oxford, England: Blackwell Scientific Publications; 1992:1699-1744.
Street ME, Weber A, Camacho-Hubner C, et al. Girls with virilisation in childhood: a diagnostic protocol for investigation. J Clin Pathol. 1997;50:379-383.
Roberts J, Ludford J. Skin conditions of youths 12-17 years. data from the National Health Survey, 1966-1970. Vital Health Stat 1. 1976;11:1-66.
Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. National Center for Health Statistics. Vital Health Statistics.1999;10(200):1-212.
Lobo RA. Hirsutism, alopecia, and acne. In: Becker KL, Bilezikian JP, eds. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia, Pa: JB Lippincott Williams & Wilkins; 1995:924-940.
Kelly AP. Acne and related disorders. In: Sams WM Jr, Lynch PJ, eds. Principles and Practice of Dermatology. 2nd ed. New York, NY: Churchill Livingstone; 1996:801-818.
Landow K. Dispelling myths about acne. Postgrad Med. 1997;102:103-112.
Leyden JJ. Therapy for acne vulgaris. N Engl J Med. 1997;336:1156-1162.
Brown SK, Shalita AR. Acne vulgaris. Lancet. 1998;351:1871-1876.
Cunliffe WJ, Holland DB, Clark SM, et al. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol. 2000;142:1084-1091.
Toyoda M, Morohashi M. New aspects in acne inflammation. Dermatology. 2003;206:17-23.
Webster GF. Acne vulgaris. BMJ. 2002;325:475-479.
Koreck A, Pivarcsi A, Dobozy A, et al. The role of innate immunity in the pathogenesis of acne. Dermatology. 2003;206:96-105.
Webster GF. Acne vulgaris: state of the science. Arch Dermatol. 1999;135:1101-1102.
Thiboutot D. Hormones and acne: pathophysiology, clinical evaluation, and therapies. Semin Cutan Med Surg. 2001;20:144-153.
Akimoto N, Sato T, Sakiguchi T, et al. Cell proliferation and lipid formation in hamster sebaceous gland cells. Dermatology. 2002;204:118-123.
Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000;21:363-392.
Stewart ME, Downing DT, Cook JS, et al. Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls. Arch Dermatol. 1992;128:1345-1348.
Grumbach MM, Styne DM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: Wilson JD, Foster DW, Kronenberg HM, et al, eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: WB Saunders Company; 1998:1509-1625.
Eady EA, Cove JH. Is acne an infection of blocked pilosebaceous follicles? implications for antimicrobial treatment. Am J Clin Dermatol. 2000;1:201-209.
Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
Kim J, Ochoa M-T, Krutzik SR, et al. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. 2002;169:1535-1541.
Webster GF. Inflammatory acne represents hypersensitivity to Propionibacterium acnes. Dermatology. 1998;196:80-81.
Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research and clinical perspectives. J Invest Dermatol. 2002;119:992-1007.
Hoffmann R. Enzymology of the hair follicle. Eur J Dermatol. 2001;11:296-300.
Cunliffe B. Acne. diseases of the skin and their treatment. Pharmaceut J. 2001;267:749-752.
Mercurio MG, Gogstetter DS. Androgen physiology and the cutaneous pilosebaceous unit. J Gend Specif Med. 2000;3:59-64.
Imperato-McGinley J, Gautier T, Cai LQ, et al. The androgen control of sebum production. studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab. 1993;76:524-528.
Lucky AW, Biro FM, Simbartl LA, et al. Predictors of sever- ity of acne vulgaris in young adolescent girls: results of a five-year longitudinal study. J Pediatr. 1997;130:30-39.
Fritsch M, Orfanos CE, Zouboulis CC. Sebocytes are the key regulators of androgen homeostasis in human skin. J Invest Dermatol. 2001;116:793-800.
Jakubovic HR, Ackerman AB. Structure and function of skin. In: Moschella SL, Hurley HJ, eds. Dermatology. 2nd ed. Philadelphia, Pa: WB Saunders Company; 1985:1-74.
Proksch E, Holleran WM, Menon GK, et al. Barrier function regulates epidermal lipid and DNA synthesis. Br J Dermatol. 1993;128:473-482.
Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res. 1991;24:1-26.
Hanley K, Rassner U, Jiang Y, et al. Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat: acceleration by estrogen and delay by testosterone. J Clin Invest. 1996;97:2576-2584.
Kao JS, Garg A, Mao-Qiang M, et al. Testosterone per- turbs epidermal permeability barrier homeostasis. J Invest Dermatol. 2001;116:443-451.
Downing DT, Stewart ME, Wertz PW, et al. Essential fatty acids and acne. J Am Acad Dermatol. 1986;14:221-225.
Melnik B, Kinner T, Plewig G. Influence of oral isotretinoin treatment on the composition of comedonal lipids: implications for comedogenesis in acne vulgaris. Arch Dermatol Res. 1988;280:97-102.
Yamamoto A, Takenouchi K, Ito M. Impaired water barrier function in acne vulgaris. Arch Dermatol Res. 1995;287:214-218.

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.

References

Ebling FJ, Cunliffe WJ. Disorders of the sebaceous glands. In: Champion RH, Burton JL, Ebling FJ, eds. Textbook of Dermatology. 5th ed. Oxford, England: Blackwell Scientific Publications; 1992:1699-1744.
Street ME, Weber A, Camacho-Hubner C, et al. Girls with virilisation in childhood: a diagnostic protocol for investigation. J Clin Pathol. 1997;50:379-383.
Roberts J, Ludford J. Skin conditions of youths 12-17 years. data from the National Health Survey, 1966-1970. Vital Health Stat 1. 1976;11:1-66.
Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. National Center for Health Statistics. Vital Health Statistics.1999;10(200):1-212.
Lobo RA. Hirsutism, alopecia, and acne. In: Becker KL, Bilezikian JP, eds. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia, Pa: JB Lippincott Williams & Wilkins; 1995:924-940.
Kelly AP. Acne and related disorders. In: Sams WM Jr, Lynch PJ, eds. Principles and Practice of Dermatology. 2nd ed. New York, NY: Churchill Livingstone; 1996:801-818.
Landow K. Dispelling myths about acne. Postgrad Med. 1997;102:103-112.
Leyden JJ. Therapy for acne vulgaris. N Engl J Med. 1997;336:1156-1162.
Brown SK, Shalita AR. Acne vulgaris. Lancet. 1998;351:1871-1876.
Cunliffe WJ, Holland DB, Clark SM, et al. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol. 2000;142:1084-1091.
Toyoda M, Morohashi M. New aspects in acne inflammation. Dermatology. 2003;206:17-23.
Webster GF. Acne vulgaris. BMJ. 2002;325:475-479.
Koreck A, Pivarcsi A, Dobozy A, et al. The role of innate immunity in the pathogenesis of acne. Dermatology. 2003;206:96-105.
Webster GF. Acne vulgaris: state of the science. Arch Dermatol. 1999;135:1101-1102.
Thiboutot D. Hormones and acne: pathophysiology, clinical evaluation, and therapies. Semin Cutan Med Surg. 2001;20:144-153.
Akimoto N, Sato T, Sakiguchi T, et al. Cell proliferation and lipid formation in hamster sebaceous gland cells. Dermatology. 2002;204:118-123.
Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000;21:363-392.
Stewart ME, Downing DT, Cook JS, et al. Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls. Arch Dermatol. 1992;128:1345-1348.
Grumbach MM, Styne DM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: Wilson JD, Foster DW, Kronenberg HM, et al, eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: WB Saunders Company; 1998:1509-1625.
Eady EA, Cove JH. Is acne an infection of blocked pilosebaceous follicles? implications for antimicrobial treatment. Am J Clin Dermatol. 2000;1:201-209.
Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
Kim J, Ochoa M-T, Krutzik SR, et al. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. 2002;169:1535-1541.
Webster GF. Inflammatory acne represents hypersensitivity to Propionibacterium acnes. Dermatology. 1998;196:80-81.
Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research and clinical perspectives. J Invest Dermatol. 2002;119:992-1007.
Hoffmann R. Enzymology of the hair follicle. Eur J Dermatol. 2001;11:296-300.
Cunliffe B. Acne. diseases of the skin and their treatment. Pharmaceut J. 2001;267:749-752.
Mercurio MG, Gogstetter DS. Androgen physiology and the cutaneous pilosebaceous unit. J Gend Specif Med. 2000;3:59-64.
Imperato-McGinley J, Gautier T, Cai LQ, et al. The androgen control of sebum production. studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab. 1993;76:524-528.
Lucky AW, Biro FM, Simbartl LA, et al. Predictors of sever- ity of acne vulgaris in young adolescent girls: results of a five-year longitudinal study. J Pediatr. 1997;130:30-39.
Fritsch M, Orfanos CE, Zouboulis CC. Sebocytes are the key regulators of androgen homeostasis in human skin. J Invest Dermatol. 2001;116:793-800.
Jakubovic HR, Ackerman AB. Structure and function of skin. In: Moschella SL, Hurley HJ, eds. Dermatology. 2nd ed. Philadelphia, Pa: WB Saunders Company; 1985:1-74.
Proksch E, Holleran WM, Menon GK, et al. Barrier function regulates epidermal lipid and DNA synthesis. Br J Dermatol. 1993;128:473-482.
Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res. 1991;24:1-26.
Hanley K, Rassner U, Jiang Y, et al. Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat: acceleration by estrogen and delay by testosterone. J Clin Invest. 1996;97:2576-2584.
Kao JS, Garg A, Mao-Qiang M, et al. Testosterone per- turbs epidermal permeability barrier homeostasis. J Invest Dermatol. 2001;116:443-451.
Downing DT, Stewart ME, Wertz PW, et al. Essential fatty acids and acne. J Am Acad Dermatol. 1986;14:221-225.
Melnik B, Kinner T, Plewig G. Influence of oral isotretinoin treatment on the composition of comedonal lipids: implications for comedogenesis in acne vulgaris. Arch Dermatol Res. 1988;280:97-102.
Yamamoto A, Takenouchi K, Ito M. Impaired water barrier function in acne vulgaris. Arch Dermatol Res. 1995;287:214-218.

The Pathophysiology of Acne Vulgaris in Children and Adolescents, Part 1

References

Pages

Recommended Reading