Stress^2 + Hormones^2 = Acne^2

By Warren R. Heymann, MD
June 5, 2019
Vol. 1, Issue 13

I would wager that every human being has experienced at least one pimple attributed to stress. I recall a devastatingly embarrassing moment during 10th grade world history class at Martin Van Buren High School (Queens, New York), when a horrific acne cyst on my neck erupted in Vesuvian fashion, necessitating my running out of the room. The physical and emotional scars remain. Aside from the usual social challenges confronted by most adolescents, I was also stressed by algebra, geometry, and trigonometry. At an early age I learned of the bidirectional nature of stress and acne — stress aggravates acne, while acne exacerbates stress. These unpleasant memories flooded back to me after reading about a novel approach to stress management — the Pythagorean Self-Awareness Intervention (PSAI).

In case you have forgotten, the Pythagorean Theorem is a² + b² = c², stating that the square of the hypotenuse (the side opposite the right angle) is equal to the sum of the squares of the other two sides. Pythagoras was also an advocate of practicing periods of silence, meditation, and self-introspection, hence the name PSAI.

Stress results in a complex interplay between the skin, neuroendocrine, and immune systems. Activation of the hypothalamic-pituitary-adrenal axis is the predominant adaptive response to systemic stress, resulting in the secretion of adrenal androgens, causing sebaceous gland hyperplasia. Corticotropin-releasing hormone (CRH) also induces proinflammatory cytokine production (IL-6 and IL-11) which are involved in the pathogenesis of acne. (1) Additionally, the neuropeptide Substance P induces inflammation by modulating the release of proinflammatory cytokines and chemokines, along with stimulating the proliferation and differentiation of sebaceous glands, thereby increasing lipid synthesis. (2)

Zari and Alrahmani performed a cross-sectional study of 144 sixth-year female medical students ages 22 to 24 attending the medical faculty at King Abdulaziz University. This study used the global acne grading system (GAGS) to assess acne severity in relation to stress using the Perceived Stress Scale (PSS). The questionnaire also included some confounding factors involved in acne severity (menstruation, heat and humidity, sweating, use of makeup and cosmetic products, oily hair products, topical steroids, and manipulation of acne lesions). Results indicated an increase in stress severity strongly correlated with an increase in acne severity, which was statistically significant (p<0.01). Subjects with higher stress scores, determined using the PSS, had higher acne severity when examined and graded using the GAGS. The authors concluded that stress positively correlates with acne severity. (1)

In a letter to the editor regarding Zari and Alrahmani, medical students Maleki and Khalid stated: “As medical students in our clinical years, we ourselves are subject to high levels of stress, and have experienced first-hand the effectiveness of stress-reduction techniques in our curriculum via student selected components (SSCs) at Barts and The London School of Medicine. SSCs, such as Mindfulness and Clinical Hypnosis, focus on developing a greater understanding and awareness of when we are stressed and recommend a variety of stress management tools. These relaxation techniques can reduce anxiety and improve overall mental health, which is also strongly linked to higher academic performance.” (3)

PSAI is practiced twice per day in a quiet place at home. At bedtime patients follow three cognitive processes. Firstly, the patient recalls every daily event in the exact time sequence that it happened. To facilitate recall, events are categorized as follows: diet (e.g., type, quantity), physical exercise (e.g., type, hours), sleep (e.g., easiness to fall asleep, duration of sleep in the previous day) and interpersonal contacts (e.g., conflicts, emotional expression, discussions etc.). In the second step each selected experience is critically appraised using three questions: ‘Is what I have done wrong? Is what I have done right? What have I omitted that I ought to have done?’ The individual is advised to remain detached from any emotional burden and contemplate on the performed actions, based on his/her own judgement criteria. Through positive (rejoice) and negative (reprimand) self-reinforcement, the individual is asked to set specific goals for the next day during the morning practice, after recapitulating the previous night’s results, without repeating the procedure. PSAI is taught by experienced health professionals. For patients with multiple sclerosis, PSAI patients have been demonstrated to have statistically significant beneficial changes in cognitive speed processing, verbal memory, stress, anxiety, depression, and fatigue.(4) For patients with chronic insomnia, PSAI has demonstrated significant improvements in sleep quality, cognitive function, cortisol levels, and perceived stress. (5) 

Chatzikonstantinou et al performed a two-armed 1:1 randomized, non-blind, eight-week experimental study of PSAI in patients with acne vulgaris (AV). The total sample was comprised of 15 female patients in the intervention group (mean age 27.2 ± 6.6) and 15 female patients in the control group (mean age 29.1 ± 6.9). Measurements included clinical stage of AV, acne-related quality of life, perceived stress, and positive and negative affect assessed by validated self-administered tools. Fourteen (93.3%) patients in the intervention group and four (26.7%) patients in the control group showed a statistically significant improvement of the acne stage. Large to moderate significant effects were observed for perceived stress and negative affect. There were no dropouts or side effects in the PSAI group. The authors concluded that PSAI may be an effective stress management method for AV, encouraging larger and longer randomized controlled studies.

The purpose of this commentary is not to advocate PSAI per se, but rather serve as a reminder to address the psychologic components of stress in acne. It is very easy to focus on the dosing of doxycycline or adverse reactions of isotretinoin. Dermatologists should inquire about what stressors aggravate a patient’s acne, and ask how patients are coping with the perceived stress. A key to improving our patients’ skin may involve addressing their psyche first. 

Point to remember: Stress management may be valuable in treating our acne patients. 

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Our expert’s viewpoint

Rick Fried, MD, PhD
Dermatologist/clinical psychologist
Clinical director
Yardley Dermatology Associates
Yardley Clinical Research Associates

Sulzberger in 1948 with passion and now Heymann in 2019 with compassion and data remind us of the protean and lasting impact of acne vulgaris and its reciprocal relationship with stress. Zari and Alrahmani’s data supporting stress as an exacerbating factor in acne severity buttresses our existing data. More importantly, they demonstrated that incorporation of an eight-week stress management program (Pythagorean Self-Awareness Intervention) into daily life resulted in statistically significant improvements in acne, stress, and negative affect. Therefore, clinicians should be compelled and empowered to briefly inquire about how their patients are coping with their life stresses. This need not open a Pandora’s box of a litany of problems for “us” to solve. Rather, it can afford us with an opportunity to succinctly offer effective stress management techniques such as the Pythagorean Self-Awareness Intervention or other proven techniques such as Jon Kabat-Zinn’s mindfulness meditation. The inquiry will likely elevate their perception of the clinician’s empathy while simultaneously offering them offering them concrete tools for stress management. I just took a long deep breath and my skin is feeling better already!

1. Zari S, Alrahmani D. The association between stress and acne among female medical students in Jeddah, Saudi Arabia. Clin Cosmet Investig Dermatol 2017; 10: 503-506. 
2. Rokowska-Waluch A, Pawlaczyk M, Cybulski M, Żurawski J, et al. Stressful events and serum concentration of Substance P in acne patients. Ann Dermatol 2016; 28: 464-469. 
3. Maleki A, Khalid A. Exploring the relationship between stress and acne: A medical student’s perspective. Clin Cosmet Investig Dermatol 2018; 11: 173-174. 
4. Anagnostouli M, Babili I, Chrousos G, Artemiadis A, Darviri C. A novel cognitive-behavioral stress management method for multiple sclerosis. A brief report and observational study. Neurol Res 2018; 19: 1-4. 
5. Tsoli S, Vasdekis S, Tigani X, Artemiadis A, Chrousos G, Darviri C. A novel cognitive behavioral treatment for patients with chronic insomnia: A pilot experimental study. Complement Ther Med 2018; 37: 61-63. 
6. Chatzikonstantinou F, Miskedaki A, Antoniou C, Chatzikonstantinou M, et al. A novel cognitive stress management technique for acne vulgaris: A short report of a pilot experimental study. Int J Dermatol. 2019 Feb;58(2):218-220. doi: 10.1111/ijd.14227. Epub 2018 Sep 19.

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