Clinics in Dermatology (2013) 31, 707–711

Psychological factors in skin diseases: Stress and skin: Facts

and controversies
Edith Orion, MD a,b,⁎, Ronni Wolf, MD a
a
The Dermatology Unit, Kaplan Medical Center, Rehovot, Israel, 76100
b
The Psychodermatology Clinic, Kaplan Medical Center, Rehovot, Israel, 76100

Abstract Psychological stress (PS) has long been related to many common skin diseases and conditions,
thought to be the cause of their onset or aggravation. Although clinical experience is often in
concordance with this notion, apparently scientific proof can sometimes be challenging rather than
straight forward. Although many data have been published, it appears that not enough good statistical
evidence exists to support them. The difficulty in validating beyond a doubt the stress–skin interactions
has rendered some skepticism among physicians.
The gap between clinical expertise and problematic clinical research data has led scientists to bypass
the need to tackle the question directly by searching the evidence in basic science.
© 2013 Elsevier Inc. All rights reserved.

Stress and skin: The paradigm What do we mean when we say

“psychological stress”?
Skin diseases, especially the more common ones, such as
psoriasis, atopic dermatitis, and alopecia areata, are widely
The presence of a force that threatens to disrupt the
associated with psychosocial problems, such as mood and
organism's homeostasis is perceived as a stressor.4 PS occurs
anxiety disorders, basically as a result of the skin condition
when an individual perceives that environmental demands
itself.1 Stress also is widely considered the most popular
tax or exceed his or her adaptive capacity.3 PS is a physio-
psychological etiology for the onset, exacerbation, and
logic process. The human body and mind react to stress by
reoccurrence of many skin conditions2 by lay people and
activating an array of physiologic and behavioral central
patients, as well as by physicians. Many patients report such
nervous system and peripheral adaptive responses, which, if
an association to their doctors, and as a result, many doctors
inadequate or excessive and/or prolonged, may affect
ask directly for stress and stressful life events when taking
personality development and behavior, and may have
their patients' disease history, thus anchoring this connection
adverse physiologic consequences.5,6 The principal effectors
in their patients' minds.
of the stress system include corticotropin-releasing hormone,
Despite this widespread belief that PS leads to disease, the
arginine vasopressin, and glucocorticoids, also known as the
biomedical community remains skeptical of this conclusion.3
hypothalamic–pituitary–adrenal (HPA) axis, and the cata-
cholamines norepinephrine and epinephrine.5 Cortisol, the
primary effector of HPA activation, regulates a broad range
⁎ Corresponding author. Fax: + 972 3 6436086. of physiologic processes, including anti-inflammatory re-
E-mail address: [email protected] (E. Orion). sponses, carbohydrate metabolism, and gluconeogenesis.3

0738-081X/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
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708 E. Orion, R. Wolf

The glucocorticoids and catecholamines affect major individual's subjective stress experiences and his or her
immune functions such as antigen presentation, leukocytes evaluation of his or her own ability to cope with the
proliferation and traffic, secretion of cytokines and anti- perceived stress posed by the events or experiences.8,10
bodies, and shifts between T-helper (Th)1 and Th2 re- The tools by which stress is measured are questionnaires
sponses, 5 thus having the potential to affect chronic and interviews; therefore, their limitations (bias, cultural
inflammatory skin diseases. differences, etc.) are inherent. Many questionnaires were
When physicians and patients talk about stress in relation developed over the past decades in an attempt to measure
to skin diseases, they usually refer to “chronic PS,” which is stress. Each “pathway” or “tradition” has its own research
known to have adverse effects on health, favor progression of questionnaire that was changed and evolved over the years to
infections, and alter immunity.7 make them better and more accurate10; nevertheless, each
type of stress measurement has its own drawbacks as
research tools in psychosomatic medicine,11 thus giving rise
Stress and skin: Can the relationship to skepticism and disparagement by some clinicians and
researchers.
be measured?
The environmental pathway records stress exposure by
giving the participants lists of critical life events; they are
If the psychophysiologic relations between stress and skin asked to report whether they have experienced any of the
conditions are so obvious in everyday clinical practice, it is events during a defined period. For each change, a score is
not surprising that the literature is packed with numerous assigned based on population studies, and a total unit sum
case reports, case series, and many studies trying to prove can be calculated.12 The life events structured interviews
this connection,2,8 whereas new studies keep appearing in were later introduced allowing the understanding of the
print every other day. context in which life events occur.10 By using these tools,
How can one prove that what most patients and doctors stress research has shown an inconsistent picture of the
accept and acknowledge is really true? If this stress–skin effects of life events or daily hassles on health.
connection is so obvious in clinical practice, why do we have Empirical studies have shown many examples in which an
such a large body of work that, at least in part, repeats itself? experience of accumulated or chronic stress led to physical
After all that is said and done, does research really prove this health problems, whereas others could not predict illness to
connection beyond a doubt? Unlike other areas in dermatol- the same extent10; moreover, in addition to life events, other
ogy, where one can quantitatively measure, for example, the sources of stress such as daily hassles, as well as enduring
effect of a drug or a procedure on a tissue, in the field of economic, work, health, or family problems, are not included
psychosomatic medicine other measuring tools are used. in the checklist of life event questionnaires or interviews, and
These research tools have their limits, thus opening the door they require a specific measurement instrument. Also, by
to skepticism among a vast majority of physicians who are definition, not all possible life events can be included in a
used to rely on other standards of research. questionnaire. That is, in part, the reason why, historically,
stress definitions have become more strongly focused on the
Stress measurements subjective reactions to external events or demands rather
than on objective events, and new questionnaires were
The effect of stress on skin conditions and diseases has developed to measure “perceived stress.” These question-
been mentioned numerous times in the medical literature in naires aimed at putting the focus on the individual's
the form of case reports and case series,9 but an objective subjective perception and emotional response,11,13 and they
research tool was needed in order to prove this alleged effect. focus on a more cognitive appraisal of stress and the
As stress is a key concept in psychosomatic medicine, individual's perceived control and coping capabilities.
measurements of stress were much investigated and much Also, of interest is the fact that most research connecting
debated.10 Apparently, there is no consensus as to how it stress and skin diseases (basically psoriasis and atopic
should be measured. Over time, measuring stress was dermatitis, but also some other skin conditions), was done
developed in basically two major “pathways”: (1) measuring retrospectively, thus is prone to biased recall. Evidence for
external stressors in terms of environmental “objective” a prospective relationship between stressors and disease
conditions and life events, and (2) measuring the person's outcome was only scarcely investigated, and in a very limited
own reaction to stress, the individual's sense of control, and extent.14,15 Although biased recall may not be a problem in
coping ability.10 the format of prospective studies, suggestibility of patients
The “environmental pathway,” which historically devel- toward their symptoms may well be, so theoretically
oped first, focuses on more specific external events or imperfections can be an integral part also in prospective
experiences that are commonly associated with considerable studies.
adaptive demands from the individual, with an emphasis on Picardi et al,8 in their eye-opening concise critical
the objective stressfulness of such events.10 The second overview on stress measurements in skin diseases state that
pathway focuses on the psychology of the individum: “although a great number of papers on this subject have been
Psychological factors in skin diseases: Stress and skin: Facts and controversies 709

published, unfortunately there appears to be a paucity of well. Acute PS can inhibit recovery of skin barrier function
controlled studies adopting standardized methods for in humans, as physiologic stress does,19 as well as affect skin
measuring stress.” We believe that although this is a true permeability homeostasis, and so on.8 Stress also can affect
problem, even in the best of hands, implementing the most the antimicrobial properties of the epidermal barrier.18
meticulous study design, there always will be drawbacks and Sustained PS compromises host defenses against bacterial
pitfalls inherent to the tools used. Picardi et al8 also stated and viral infections in humans and in experimental
that after critically reviewing all data, the role of stressful animals.20,21 The implications of all these findings are
events in psoriasis, alopecia areata, atopic dermatitis, and obvious considering psoriatic or atopic skin.
urticaria is probably confirmed. Although serious research is being done in this field, many
Apparently, there are limits to clinical research in this field, key issues of understanding the exact mechanisms of the
as probably exist in other fields of psychosomatic medicine as effect of stress on epidermal barrier still need to be elucidated;
well. These limits, as well as the technical problems in nevertheless, it reinforces the validation of “skin–mind”
conducting perfect clinical trials measuring stress (or other connection, using another perspective on the issue, by
parameters in psychodermatology), should be acknowledged. implying research tools that are more familiar to clinicians
Obviously, when conducting such a trial, attention should be that are less “comfortable” with psychosomatic medicine.
given to every aspect in the patient's life (eg, skin condition,
general health, stressful events, protective and vulnerability
factors, etc.),8 as well as to the setting in which the study is
conducted, the interaction with researchers, and so on.
Understanding vulnerability to stress: Who is a
Countless parameters should be taken into consideration, susceptible to stress?
thus making such a perfect trial almost impossible to perform.
In our opinion, these difficulties and limitations should not In recent years, more studies are done focusing on the
discredit the large body of research that was done and will be next obvious questions: Can we understand why some
done in years to come, but rather encourage us to judge it with a patients are more resilient to stress than others? Can we map
different perspective than we are used to. the major “roads” that lead to stress susceptibility?14,22,23
Can we find the common psychosocial denominators among
patients developing specific skin conditions?
Indeed, these questions reflect the simple fact that
Effect of stress on skin: Laboratory research scientists already have accepted the assumption that stress
is a true factor in the development and progression of some
The “biological pathway” is a third way to prove the effect skin conditions, and based on that established knowledge,
of stress on the skin. It focuses on the activation of certain progression of research is on its way.
physiologic systems in response to PS, with an emphasis on Basically, stressful events are thought to influence the
the mechanism by which environmental demands may be pathogenesis of a physical disease by causing negative
translated into biological changes in the body.8 Surprisingly, affective states (eg, feeling of anxiety and stress, as well as
rather little research was done using the physiologic depression), which in turn exert direct effects on biological
mediators of stress (ie, cortisol and catacholamines), although processes and/or behavioral patterns that influence disease.24
several studies tested serum cortisol levels as possible stress Exposure to chronic stress is considered the most toxic because
markers in psoriasis, and low basal cortisol levels were it is most likely to result in long-term or permanent changes in
measured in patients with severe atopic dermatitis.16,17 the emotional, physiologic, and behavioral responses that can
Instead of measuring the stress hormone levels in patients influence susceptibility to disease development and course.24
with skin diseases, there is a growing tendency to understand A number of factors have been implied so far to affect the
this potential effect through laboratory basic research. individual psychological vulnerability to disease. Early life
Understanding the damage that stress implies on the skin events may theoretically render the individual more
in some skin diseases can help us understand the extent and vulnerable to the effects of stress in later life,25 as was
through what mechanisms this psychological, somewhat shown in animal models. Traumatic psychological events
elusive term, acts. The effect of psychological stress on the have consistently resulted in development of physiologic
epidermal barrier integrity is in the focus of research in the vulnerability such as increased HPA axis activation.25 This
past several years. These studies can prove that stress indeed pathway was not explored much in dermatologic patients,
affects the skin by bypassing the need to use the “imperfect” although some preliminary trials were done among patients
tools of psychosomatic research. with psoriasis and atopy.22,26
Stress can affect skin permeability in animals. Studies in Mapping vulnerability rendered, for example, a correla-
rodents, for example, found that imposition of different tion between high levels of worrying and scratching and the
forms of PS provoked an abnormality barrier homeostasis,18 effect of stressors on the skin disease in psoriatic patients14;
thus leading the way to studies in humans. Later, it was validation of the role of family dysfunction in the onset or the
proved that stress can affect skin permeability in humans as exacerbation of psoriasis, alopecia, and atopic dermatitis23;
710 E. Orion, R. Wolf

alexithymia, insecure attachment, and poor social support and treatment of psychosocial variables in the setting of
were found to increase susceptibility to vitiligo, possibly medical disease. Psychosomatic medicine has evolved so
through deficits in emotion regulation or reduced ability to much, that it can now appreciate a wider spectrum of factors
cope effectively with stress.27 Also, children and adolescents affecting individual vulnerability to all types of disease:
with alopecia areata were found more often to be members of recent and early life events, chronic stress and allostatic load,
a single-parent family and perceive less expressiveness personality, psychological well-being, health attitudes, and
within their family.28 behaviors.31 It provides a comprehensive framework for a
more “holistic” consideration of patient care. Psychoderma-
tology, a division of the latter, also has evolved tremendously
and can now offer a wider view and understanding of the
Evidence-based medicine patient suffering from skin disease. Psychodermatology no
and psychodermatology longer deals with mere “stress,” but acknowledges a broader
range of factors such as family dysfunction,23 self-efficacy,32
The evidence-based medicine (EBM) movement arose and so on, affecting exacerbations and reoccurrences of skin
out of concern that many patients were receiving ineffective diseases and conditions. The fact that dermatologists do not
treatments that were grounded in conventional practices, know or are interested in or appreciate the advances that
clinical intuitions, or practitioner idiosyncrasies rather than psychodermatology offers,33 especially in the field of
scientific evidence.29 This concern is still prevalent among factors, which have effects on disease/therapy outcome,
many dermatologists when discussing psychodermatology may have a negative effect on patient management, and
because many believe that some aspects in psychodermatol- therefore on patients' lives.
ogy (stress-related diseases, being one of them) have not We believe that PS should not be reduced any more by
been investigated properly. dermatologists to a generic term but rather be appreciated as
Sackett et al have defined EBM as the conscientious, an elaborate term encompassing within it an array of factors
explicit, and judicious use of current best evidence in making contributing to the development, exacerbations and to the
decisions about the care of individual patients. The practice outcomes of many common skin diseases.
of EBM means integrating individual clinical expertise with
the best available external clinical evidence from systematic
research.30
Clinical practice relies on EBM for the production of Conclusions
practice guidelines and the adoption of specific therapeutic
interventions.29 In other words, EBM deals with treatments “If it walks like a duck, quacks like a duck, looks like a
rather than with etiology (although the connection of the two duck, it must be a duck.”
is obvious). Apparently, EBM is not the appropriate term to
be used by “psychodermatology-deniers” when arguing
stress' role in skin conditions. Stress is a key topic in dermatology because the onset and/or
Has psychodermatology research evaluated the effective- exacerbations of many skin conditions are traditionally related
ness of stress reduction in the management of skin diseases? to stress. A huge effort was made to prove the effect of stress on
Surprisingly, it appears that researchers show more enthu- several common skin diseases. Problems such as inherent flaws
siasm in proving psychological difficulties to be an etiologic of the research tools (questionnaires) and paucity of controlled
factor in the onset, exacerbation, or reoccurrence of skin studies adopting standardized methods for measuring stress
diseases, but much less enthusiasm in finding whether have led to difficulties of some dermatologists to accept this
psychological therapies can ameliorate them. relationship as “legitimate.” Use of other research pathways,
Searching the medical literature, one can find only limited such as exploring the neuroimmunocutaneous reactions to PS,
data concerning psychotherapy or psychopharmacology allows bypassing the need to rely solely on psychosomatic
interventions in skin conditions; most of it is preliminary research tools that are less familiar to dermatologists. New
reports and case series. To date, we still do not know enough studies that focus on the roots of stress vulnerability provide
about how to deal with this issue, although ironically this is more information of the whole picture of stress–skin
the most important and practical question. connections but at the same time accept and validate the
notion that PS do have an effect on the skin.

Psychosomatic medicine and psychodermatology:

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