Acne & Rosacea: Just the Facts: Does Stress Cause Acne? - By Jonette E. Keri, M.D., Ph.D. As a clinician on the frontlines, I hear many of the same questions you likely hear from your patients.The purpose of this column is to give you answers, which are backed by research, to common questions concerning acne and rosacea. A question often posed to me by patients and their families or caregivers is: What role does “stress” have on “breakouts”? Answering such a question is difficult because of the many problems associated with studying such a question. First of all, how do we define “stress”? Are we talking about emotional stress, environmental stress or physical stress? Even if we use existing psychological measures to evaluate such stress, the relationship is complex and will be difficult — if not impossible — to figure out in a disease known to be multifactorial. Here, I’ll discuss what clinical and scientific data are available that show a connection between stress and acne, and I’ll talk about how I answer the question of whether stress causes acne with my patients. What Do We Know Now? It is more frequently well documented that acne causes emotional stress (reviewed by Baldwin1) rather than stress causes acne. Although it has been long observed by physicians and patients, the clear type of stress or amount of it that can cause acne remain less studied. A recent (2001) review2 by Picardi and Abeni of the literature evaluating the role of stress in skin disease found the role of stressful events in the course of acne to be insufficiently explored. This review defined more clearly the role of stress associated with psoriasis, alopecia areata, atopic dermatitis, and urticaria. Such reviews bring to the forefront the true lack of data on the subject. What clinical and scientific data do we have to relate stress to acne? • Many researchers have proposed a mechanism involving the pituitary-adrenal axis where stress causes a release of androgens from the adrenal gland. These androgens then go on to act at the level of the sebaceous gland.3 Specifically, post-adolescent acne in women has been related to chronic stress, giving rise to increased adrenal androgen.3 • Goulden4 went on to review men and women with such post-adolescent acne and found that only 12% admitted they were under chronic stress; however, the stress was not formally assessed in this study. • We do know that increased cortisol levels are observed in acne patients and have been correlated to emotional stress.5,6 An interesting example of a specific stressor giving rise to acne and endogenous hypercortisolemia was reported in a 13-year-old girl after cardiac surgery and post-operative complications.7 In addition to her acne, she also had resultant striae. In this case report, the patient received no corticosteroids, had a negative workup for an internal source of cortisol, had lab results supporting the endogenous increase in cortisol, and medications were excluded except for amiodarone (Cordarone), which could have heightened her response but is much less likely as a causative agent. Researchers concluded that the acne was a result of the increased cortisol. New Concepts in Potential Stress Inducers Many of you are familiar with the idea of adrenal androgens playing a role in acne. However, new concepts regarding stressors include the involvement of neuromediators that are released in response to stress. It has been proposed that a variety of neuroendocrine factors act centrally and locally at the level of the sebaceous gland to contribute to acne. That is to say, such neuromediators can stimulate sebum production,8,9 influence production of inflammatory reactions through cytokines, and cause sebocyte differentiation and proliferation.10,11 Specifically, substance P, a neurotransmitter, which stress can elicit, was shown by electron microscopy to act on sebaceous glands.9 The authors noted substance P increased the size of individual sebaceous cells and number of sebum vacuoles in differentiated sebaceous cells in these in vitro studies. Past Evaluations of Stress We have thrown out some ideas on pathogenesis, but how has stress been evaluated in the past? Acne as a response to a specific stress has been studied. Examination stress is a well-accepted acute form of stress that has been evaluated. In 1970, Kraus12 evaluated nine medical students exposed to an 8-hour academic exam and found that eight out of nine had increased acneiform pustules during a stressful period (comedones and papules were not assessed). More recently, Chiu, et al13 reported an increase in acne, acne severity, and perceived stress during examination periods. In this study, patients were kept on current acne medications, excluding isotretinoin (Accutane, Amnesteem, Claravis, Sotret), and were not on sedatives, antidepressants or exogenous glucocorticoids. What is interesting about this study is that even after adjusting for changes in sleep hours, perceived quality of sleep, meals per day and perceived quality of meals, an increase in stress correlated with an increase in acne severity. The acne was evaluated in a blinded fashion by a board-certified dermatologist. This study attempted to tease out some type of definition of the word “stress” by patients. Observational data have been suggested by Harrington,14 who commented on experience with female patients in whom endocrinologic workup was negative, but whom had acne and related it temporally to marital breakup. The author’s observation was that some of these patients after not responding to other treatments had their acne improve with fluoxetine (Prozac). Again, as with adult acne, there is a preponderance of women versus men reporting stress-induced acne. In the past, this adult acne or post-adolescent group of patients was thought to have a large component of acne cosmetica. Although acne cosmetica must be excluded, such post-adolescent or adult acne, as discussed above, may be associated with chronic stress. Premenstrual flares were noted in these female patients, and a recent study quantified premenstrual flares, showing that 63% of women surveyed showed a 25% increase in inflammatory lesions during this period.15 Such premenstrual flares are noted more often in older women.16 Many women would contend that the premenstrual time is indeed a stressor to them. What Do We Tell Our Patients? So we have some clinical research experience to support the role of stress (loosely defined) in the development of acne. What do we tell our patients? We educate them. We tell them that it is a commonly held belief among lay persons and physicians that stress can exacerbate acne. We can tell them that it is difficult to pinpoint which stressors contribute and how much they contribute to acne. We can encourage relaxation techniques for overall health and well being, all the while making good attempts to treat the acne and the person behind the acne. For the patient who has premenstrual or menstrual flares, pulse antibiotic dosing or oral contraceptives can be effective. Importantly, we must identify patients with anxiety, depression or other psychological conditions so that we can refer them to a psychiatrist/psychologist. This may not be easily accomplished because many patients do not want to see such practitioners. In such a scenario, engaging the patient’s primary care physician may be the best bet, unless you are comfortable treating these psychological conditions (many dermatologists are not). Finally, we must encourage patients, physicians and researchers to become involved in studies concerning stressors and acne.   References: 1. Baldwin, H.E. The Interaction between acne vulgaris and the psyche. Cutis. 2002;70(2):133-9. 2. Picardi, A., Abeni, D. Stressful life events and skin diseases: disentangling evidence from myth. Psychother Psychosom. 2001;71(2):123-6. 3. Kligman, A. M. Postadolescent acne in women. Cutis. 1991;48:75-7. 4. Goulden, V., Clark, S.M., Cunliffe, W.J. Post-adolescent acne: a review of clinical features. Br J Derm. 1996;136:66-70. 5. Schmidt, J.B., Lindmaier, A. Spona, J. Endocrine parameters in acne vulgaris. Endocrinol Exp. 1990;24:457-64. 6. Lucky, A.W., Rosenfield, R.L., McGuire, J. et al. Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism:adrenal enzyme defects and exaggerated adrenarche. J Clin Endocrinol Metab. 1986;62:840-8. 7. Goggin, N., Enright, F., Costigan, C., Duff, D., Oslizlok, P., Wood, A.E., Watson, R. Striae and acne following cardiac surgery in a child. Br J Derm. 1999;140(4):734-6. 8. Dreno, B. Pathophysiology of acne. Press Medicale. 2005;24(7):537-9. 9. Toyoda, M., Morohashi, M. Pathogenesis of acne. Medical Electron Microscopy. 2001;34(1):29-40 10. Zouboulis, CC., Bohm, M. Neuroendocrine regulation of sebocytes — a pathogenetic link between stress and acne. Experimental Derm. 2004;13 Supp 4:31-5. 11. Toyoda, M., Morohashi, M. New aspects in acne inflammation. Dermatology. 2003;206(1):17-23. 12. Kraus, S. J. Stress, acne and the skin surface free fatty acids. Psychosom Med. 1970;32(5):503-8. 13. Chiu, A., Chon, S.Y., Kimball, A.B. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stress. Arch Dermatol. 2003;139(7):897-900. 14. Harrington, C.I. Post-adolescent acne and the marital break-up. (comment). Br J Derm.1997; 137(3):478-9. 15. Lucky, A.W. Quantification of a premenstrual flare of facial acne in adult women. Arch Dermatol. 2004;140(4):423-4. 16. Stroll, S., Shalita, A.R., Webster, G.F., Kaplan, R., Danesh, S., Penstein, A. The effect of menstrual cycle on acne. J Am Acad Dermatol. 2001;45(6):957-60. Skin & Aging - ISSN: 1096-0120 - Volume 14 - Issue 10_2006 - October 2006 - Pages: -