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68
major stressful life events (eg, separation, death or illness of a loved one, and financial difficulties);
psychological (intrapsychic) or personality difficulties;
and
lack of social support.5
Significance of Stress
and Physiologic Response
Normal physiologic response to stress involves activation of
the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic adrenomedullary (SAM) axis, both of which regulate
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nificantly elevated cortisol responses to the heel prick stress
(a well-known significant stressor for the newborn) compared to controls. There was a positive correlation between
the cord IgE levels to the basal cortisol levels and the degree
of elevation in the cortisol levels in response to the stressor. A
potential link between the observations of hyperactivity in
atopic-prone newborns and hyporeactivity of the HPA axis in
long-term atopic dermatitis patients exists. In explaining the
link, it has been postulated that with the onset and/or chronification of the disease the HPA axis may switch from a hyperto a hypo-reactive state. Therefore the initial impaired hyperreactivity of the HPA axis to stressors may increase the subjects vulnerability to develop a manifestation of atopy later in
life.24 To demonstrate the latter phenomenon, children aged
9 to 14 years, with at least a 5-year history of atopic dermatitis, were subjected to a public speaking stress test. The
children with atopic dermatitis demonstrated a blunted cortisol response while the age-matched controls demonstrated
the expected elevated cortisol levels in response to stress.25
The temporal factor on disease manifestation has been suggested in psoriasis as well. It has been observed that approximately one-third of psoriasis patients manifest their disease
by the age of 15 years.24 Ferrandiz et al performed an epidemiologic study in Spain and concluded that there are 2 different groups of patients with psoriasis. Early onset psoriasis
(younger than 30 years) seemed to follow an unstable course
and showed a tendency to become severe with more extensive body surface involvement and higher Psoriasis Area and
Severity Index (PASI) scores over time compared to lateonset psoriasis.26 In another study, Gupta et al found that
psoriasis patients who exhibited early onset psoriasis (before
the age of 40 years) seemed more prone to psoriasis flares
than patients with late onset psoriasis. In 2010, Simonic et al
explored whether psoriasis was related to positive and negative traumatic life events and investigated differences between early and late onset psoriasis. The findings showed that
many psoriatic patients had histories of child and adult
abuses; and in comparison to controls, these patients had
significantly higher negative experiences. Early onset patients
had significantly higher incidents of emotional abuse, alcohol/drug abuse, and other trauma compared to the control
group. Also, late onset psoriasis patients had higher levels of
traumatic events compared to the control group. Gupta et al
found that early onset psoriasis was more often triggered by
environmental factors such as an external stress, in contrast
to late onset psoriasis. He postulated that younger populations may have greater difficulty with assertion and expression of anger, which adversely affects their ability to cope
with stress.27
Additional theories about the effect of psychological stress
exist. For example, in acne, investigators believe there is an
increased release of glucocorticoids and adrenal androgens.
Both hormones are known to worsen acne and induce sebaceous hyperplasia during emotional stress.28 In addition, it
has been postulated that the stress-induced release of neuroactive substances within the epidermis can activate inflammatory processes in the skin. Research on stress is progressing and
70
evidence that psychological stress corresponds with a pathological physiologic response continues to grow.
Stress Evaluation
Indications for evaluation include a history of stress that acts
as a trigger to the skin disorder, psychiatric comorbidities, or
significantly decreased quality of life. An effective and simple
question to initiate this conversation would be to inquire if
the patient has experienced stress and if this worsens the
severity of their skin condition. Additional questions about
stressful life events, depression, anxiety, feelings of fatigue or
helplessness, the existence of an adequate support system, or
experience with stress management strategies, will help the
physician determine how the patient is susceptible to the
pathophysiologic effects of stress. Patients should also be
taken through the assessment to uncover underlying psychiatric disorders, such as major depression or generalized anxiety, as described by the Diagnostic Statistical Manual of Mental
Disorders (4th edition) published by the American Psychiatric
Association.29 Patients with diagnosable psychiatric disorders should be advised to see a mental health professional.
Management of
Psychologic Symptoms With
Nonpharmacologic Approaches
Psychologic symptoms may be addressed with nonpharmacologic treatments. Options include cognitive behavioral
therapy, biofeedback, guided imagery, and relaxation training. It may be worthwhile to pursue psychologic treatments
in patients whose dermatologic disease remains unresponsive to treatment and an underlying emotional cause is suspected. For example, Waxman described a woman with a
20-year history of psoriasis that went unresolved until she
received 15 weeks of treatment under hypnosis incorporating analysis and discussion; and interpretive psychotherapy
and desensitization by reciprocal inhibition. At a 10-month
follow-up, she continued to remain clear.30 In a study of 72
patients with eczema, patients with emotional or psychiatric
disturbance had improved outcomes with the addition of
psychiatric treatment devised specifically for the study patient. In comparison, those who did not have additional psychiatric treatment did not have improved outcomes.31 Stewart et al studied 18 adults with atopic dermatitis who had
been resistant to conventional topical therapies and antihistamines. The subjects were treated with the addition of psychological treatment such as relaxation and stress management. They showed statistically significant improvement of
itching and scratching, sleep disturbance, and mood.32
Children and adolescents, in particular, may benefit from
psychologic intervention. Psychologic disorders and comorbidities may impair growth during the developmental period.
In cases where psychological causes have yet to be discovered, psychological intervention may still be beneficial in
guiding behavioral development in children and demonstrat-
identify specific maladaptive patterns through the patients verbalization of thoughts and feelings or by direct observation of behavior;
determine the goals of therapy;
develop a hypothesis for underlying beliefs or triggers
that provoke maladaptive thought patterns and behavior;
test the hypothesis by altering cognition, behavior, or
environment and observe the effects; and
revise the hypothesis if desired results are not obtained.
Management with
Pharmacologic Approaches
When appropriate, pharmacologic agents may be beneficial
to patients. Pharmacologic therapies may be considered if
nonpharmacologic therapies were inadequate for treatment,
if the patient does not have the time to carry out a nonpharmacologic approach, or if the combination of treatment
approaches may yield better results. A collaborative effort
between clinicians managing the patient (for example, a dermatologist and a psychiatrist) may help guide treatment.
However, some patients may resist seeking management
from psychiatric care. Therefore, clinicians, such as dermatologists or general practitioners, may need to provide treatment alone. Prior to starting therapy, an initial psychiatric
evaluation may help clinicians choose the most appropriate
category of psychopharmacologic agents.
Antidepressants include selective serotonin reuptake inhibitors (SSRIs), tricyclics, monoamine oxidase inhibitor,
and buproprion. There are reports regarding positive results
with the use of SSRIs in dermatology. DErme et al found
statistically significant improvement in psycho-diagnostic
test scores in patients with moderate to severe plaque psoriasis treated with anti-TNF agents receiving adjunct treatment with escitalopram (Lexapro) in comparison to control
groups with only anti-TNF. Although the study did not
observe a noticeable reduction in clinical severity of psoriasis,
psychological intervention led to perceived improvements in
symptom severity, quality of life, and compliance to treatment.37 In another study, Mitra et al found patients who were
receiving fluoxetine (Prozac) in addition to PUVA treatment
had enhanced response and quicker remission as compared
to the patients receiving PUVA alone.38 Moussavian reported
improvement of acne in depressed patients (2 adults and 5
adolescents) treated with paroxetine (Paxil).39 Stnder et al
evaluated the effect of paroxetine and fluvoxamine (Luvox) in
72 pruritic patients and found that the best antipruritic response with these agents was observed in patients with atopic
dermatitis, systemic lymphoma, and solid carcinoma.40 SSRIs
are also preferred because of greater tolerability and the safety
profile in comparison to other antidepressants. However, it
should be mentioned that there are also rare case reports,
which associate SSRIs with flares in psoriasis.41-43
Buproprion-SR (Welbutrin) may be effective for nondepressed individuals. Modell et al treated 10 nondepressed
atopic dermatitis patients and 10 nondepressed psoriasis patients. Six of 10 atopic dermatitis patients and 8 of 10 psoriasis patients responded to 150 mg/day for 3 weeks followed
by 300 mg/day for 3 more weeks. Baseline measures improved after 6 weeks of therapy and average body surface
area involvement was reduced by roughly 50% in both
groups. The therapeutic effect was further supported when
the 8 responders discontinued buproprion-SR and disease
severity worsened within 3 weeks.44 Gonzlez reported on an
individual in their study suffering from severe atopic dermatitis without psychiatric symptoms who was treated with buproprion and had a very good response.45
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Some tricyclic antidepressants are effective for symptomatic relief of pruritic symptoms due to the histamine H1
blocking effect46 but caution needs to be exercised due to the
potential for a lethal overdose.
Anti-anxiety medication could be potential treatment options for short-term use during stressful situations. Alprazolam (Xanax) is a rapid-acting medication with both antidepressant and antianxiety effects. The combined effect may
be beneficial and, with a shorter and more predictable halflife, would lead to less risk and concern for systemic accumulation over time and subsequent side effects. However,
alprazolam may be sedating (depending on the dose used)
and potentially addictive.
Conclusion
Emotional stress is commonly accepted as an exacerbating
factor in the disease state of inflammatory skin disorders.
Many clinical studies continue to document its role in the
onset and exacerbation of skin disorders such as psoriasis,
eczema, and acne. Management of skin disorders may be
optimized by nonpharmacological- or pharmacological-psychological intervention.
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