Stress as an Influencing Factor in Psoriasis

Misha M. Heller, BA¹, Eric S. Lee, BS², and John Y.M. Koo, MD³

¹ Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
² College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
³ Department of Dermatology, Psoriasis and Skin Treatment Center, University of California, San Francisco, CA, USA

ABSTRACT
Emotional stress may influence the development and exacerbation of psoriasis. The proportion of psoriasis patients who believe stress affects their skin condition (i.e., “stress responders”) is considerably high, ranging from 37% to 78%. Stress may worsen psoriasis severity and may even lengthen the time to disease clearance. Although a pathogenic association appears likely, additional well-controlled studies are necessary to confirm such a causal relationship. Dysregulation of the hypothalamus-pituitary-adrenal and sympathetic adrenomedullary systems has been proposed as one possible underlying cause of stress-induced flares of psoriasis. While stress may be an exacerbating factor, psoriasis itself may contribute to significant adverse psychological sequelae. Breaking this stress cycle may be an important part of any therapeutic approach. Thus, stress reduction through psychotherapy and pharmacotherapy may be useful in treating psoriatic patients who are stress responders.

Key Words:
anxiety, depression, chronic inflammatory disease, psoriasis, stress

Psoriasis is a chronic, inflammatory skin disease with an approximate 2-3% prevalence in the general population.¹ The etiology of psoriasis is not fully understood, but it appears to be multifactorial, involving both genetic and environmental influences. Among these factors, emotional stress (hereafter simply referred to as “stress”) is considered to play an important role in the onset and exacerbation of psoriasis.²

Stress has been indicated as a trigger in many dermatologic conditions, including atopic dermatitis, acne vulgaris, and chronic urticaria. With each of these conditions, one encounters both patients who experience a close chronologic association between stress and exacerbation of their skin disease, and patients for whom their emotional states seem to be unrelated to the natural course of their cutaneous disorder. These two groups are considered “stress responders” and “non-stress responders,” respectively.³

Just as in many dermatologic conditions, psoriasis appears to worsen with stress in a significant segment of patients. Studies report that the proportion of psoriasis patients who are stress-responders ranges from 37% to 78%.⁴

Significance of Stress

Studies define stress along three general categories: 1) major stressful life events (e.g., change of employment, major personal illness, financial problems), 2) psychological or personality difficulties, and 3) lack of social support.⁵ Regardless of how stress is defined, studies consistently support a relationship between stress and psoriasis.^5-12 Furthermore, a majority of patients consider stress to be the main cause for exacerbation of their psoriasis, ranking it above infections, trauma, medications, diet, or weather.⁶

For example, Seville⁷ examined 132 psoriasis patients whose psoriasis had completely cleared with anthralin therapy and were followed over 3 years. Fifty-one patients (39%) recalled specific incidents of stress within 1 month prior to psoriasis exacerbation. The study further observed that the incubation time from specific incidents of stress to psoriasis exacerbation was between 2 days to 1 month.⁷ In a subsequent study, Al’Abadie et al.8 assessed 113 psoriasis patients and determined the incubation time from stressful event to onset of psoriasis was significantly longer than that from stressful event to exacerbation of psoriasis.⁸

In a study of 127 psoriasis patients, Gupta et al.5 found differences between patients who reported that stress flared their psoriasis (stress responders) and patients who reported no association (non-stress responders). Stress-responders described significantly more flare-ups during the 6 months prior to admission, experienced more psoriasis-related daily stress, and relied more upon the approval of others. They also had more severe psoriasis in “emotionally charged” body areas, such as the scalp, face, neck, forearms, hands, and genital region. However, total percentage of body surface affected by psoriasis was not significantly different.

Similarly, Zachariae et al.9 showed that stress responders differed significantly from non-stress responders. Stress responders tended to self-report greater disease severity than non-stress responders, even though clinical measures of disease severity (e.g., Psoriasis Area Severity Index) did not vary between groups. Stress responders were, however, found to have more plaques of psoriasis on visible areas than non-visible regions.⁹

Unlike these above studies, Verhoeven et al.10 found a significant association between stress and disease severity. This prospective study of 62 psoriasis patients determined high levels of daily stressors to be related to an increase in disease severity 4 weeks later.¹⁰

Finally, stress may not only worsen psoriasis severity, but it may also adversely affect treatment outcomes. Fortune et al.¹³ found that psychological stress impaired the rate of clearance of psoriasis in patients undergoing psoralen + ultraviolet A (PUVA) treatment. Patients with high-levels of worry cleared with PUVA therapy almost two times slower than those with low-levels of worry.¹³

Physiologic Effects of Stress

Normal physiologic response to stress involves activation of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic adrenomedullary (SAM) axis, both of which interact with immune functions. Generally, in normal individuals, stress elevates stress hormones (i.e., increases cortisol levels). However, according to available studies, exposure to stress in psoriatic patients has been associated with diminished HPA responses and upregulated SAM responses.^14-17 More specifically, when psoriasis sufferers are under such emotional pressures lower plasma cortisol levels14 and higher epinephrine and norepinephrine levels¹⁵ can be induced, when compared with controls.

Similarly, Evers et al.16 found psoriasis patients had significantly lower cortisol levels at moments when daily stressors are at peak levels. The study also reported that psoriasis patients with overall high levels of daily stressors exhibited lower mean cortisol levels, as compared to psoriatics with overall low levels of daily stressors.¹⁶ Furthermore, Richards et al.¹⁷ observed physiologic differences in response to stress between psoriasis patients who are stress responders and those who are non-stress responders. Specifically, stress-responders had lower salivary and serum cortisol levels than non-stress responders following a social performance stressor.¹⁷

These blunted HPA axis and elevated SAM system responses to stress may be crucial in better understanding the inflammatory characteristics of psoriasis, particularly in stress-responders. For instance, decreased secretion of cortisol and increased levels of epinephrine and norepinephrine may stimulate the release of mast cells, affect skin barrier function, and upregulate proinflammatory cytokines, which could thereby maintain or exacerbate psoriasis severity.¹⁶ Some authors have commented that this decreased cortisol response may be similar to how psoriasis flares with steroid withdrawal, as evidenced by the well known phenomena of steroid-induced psoriasis rebound.¹⁷

Stress and Psoriasis: A Vicious Cycle

Psoriasis itself can serve as a stressor for patients. Psoriasis can be a disfiguring skin disease with much attached social stigmata. Accordingly, patients often suffer significant interpersonal and psychological distress. Patients commonly experience difficulties in social interactions, especially in meeting new individuals and forming romantic relationships. In general, most patients demonstrate adverse psychological consequences, including poor self-esteem, anxiety, depression, and for some, even develop suicidal ideation.¹⁸

As psoriasis can cause considerable stress for patients and increased levels of stress are likely to exacerbate psoriasis, the disease process, thus, becomes a self-perpetuating, vicious cycle.¹⁹ Therefore, treatment considerations for psoriasis should integrate methods of stress reduction, including psychotherapy and pharmacotherapy, especially for known stress responders.

Stress Evaluation and Management

The best approach to evaluating if an individual is a stress responder is to simply ask the patient, “Do you believe stress frequently worsens the severity of your psoriasis?” If the patient answers “yes” to this question, a clinician may want to consider further evaluating the impact of stress on the patient’s life. Useful questions may include: Have you experienced any recent stressful life events? Do you feel depressed or anxious? Do you have friends or family members that provide you with adequate social support? Do you feel you can manage the level of stress in your life? Ultimately, these questions should help guide a treating physician in determining if their patient is a stress responder. However, a clinician should be cognizant that the terms “stress responder” versus “non-stress responder” only refer to whether or not the patient’s psoriasis worsens with emotional stress. These terms do not indicate whether or not the patient has an underlying diagnosable psychiatric disorder, which is a separate issue requiring an alternate clinical approach.

As such, it is important to determine if the patient meets the diagnostic criteria for major depression, generalized anxiety, or other psychiatric disorders, as described by the Diagnostic and Statistical Manual of Mental Disorders (4th edition) published by the American Psychiatric Association.20 Obviously, all patients with diagnosable psychiatric disorders should be advised to seek appropriate mental health care. As for patients who are stress responders, but are otherwise psychologically well-functioning individuals, they should be made aware of the potential benefits of stress reduction in improving their skin condition. Some relatively easy and feasible stress reduction techniques are yoga, deep breathing exercises, and meditation, just to name a few. More intensive approaches to stress reduction, like psychotherapy or pharmacotherapy, may also be reasonable recommendations. Whether a patient is simply experiencing situational stress or suffering from a diagnosable psychiatric disorder, it may be advisable for that individual to consult a mental health professional as long as emotional factors (such as stress) play an important role in the natural history of their psoriasis.

Therapeutic Overview

Psychotherapy and Stress Reduction

Psychotherapy may be beneficial for psoriasis patients. Seng et al.²¹ found group therapy to be a useful and supportive treatment. Group therapy provided patients with knowledge about psoriasis and helped them better cope with their skin disease. Talking to other psoriasis patients enabled participants to learn how to manage disease-related stress and gain self-confidence.²¹

Case reports have described improvements in psoriasis severity with relaxation and stress reduction techniques, such as hypnosis and thermal biofeedback.^22,23 Likewise, Price et al.24 showed the potential efficacy of psychotherapy in a study of 11 patients, who completed an eight-session intervention consisting of relaxation and cognitive techniques. Patients reported a significant reduction in levels of anxiety and showed improvements in psoriasis severity based on a visual-analogue scale examining area of involvement, erythema, induration, and scaling.²⁴

Additionally, in a study of 37 patients treated with ultraviolet B (UVB) or PUVA therapy, Kabat-Zinn et al.²⁵ found that stress reduction may help accelerate the rate of clearance. Patients were randomly assigned to either an audiotape-guided, meditative stress reduction exercise during the light treatment, or a control group consisting of the light treatment alone. Study findings revealed that patients in the stress reduction group reached the clearing point (or the point at which less than 5% of the baseline level of psoriasis remained) more rapidly than controls in both UVB and PUVA therapies.²⁵

Pharmacotherapy and Stress Reduction

Pharmacotherapy may also be a helpful adjunct to psoriasis treatment. Studies have demonstrated improvements in psoriasis with oral administration of antidepressants, such as the tricyclic antidepressant (TCA) imipramine (Tofranil®), the monoamine-oxidase inhibitor (MAOI) moclobemide (Manerix®), and buproprion-SR (Wellbutrin®).^26-29

Modell et al.²⁹ found that the norepinephrine-dopamine uptake inhibitor buproprion-SR may be effective in treating non-depressed individuals with psoriasis. Ten patients were given buproprion-SR monotherapy at 150 mg/day for 3 weeks, and then increased to 300 mg/day for 3 more weeks. Only one patient remained on 150 mg/day dosing for all 6 weeks. Eight out of the 10 patients showed improvement from baseline after 6 weeks of therapy, with an average body surface area reduction of about 50%. Of these eight responders, disease severity worsened (towards pre-study baseline psoriasis coverage) within 3 weeks of discontinuing buproprion-SR.²⁹

In contrast, there are also a total of six cases reporting that the selective-serotonin reuptake inhibitors (SSRIs) fluoxetine (Prozac®) and paroxetine (Paxil®) may induce or exacerbate psoriasis.^30-32

Pharmacologic Treatment Recommendations

When pharmacologic treatment is deemed appropriate for stress reduction, SSRIs should be considered for first-line therapy. Despite the six reported cases of SSRI-associated flares of psoriasis,30-32 SSRIs have certain merits in the treatment of psoriasis patients experiencing depression. As well, these agents may possibly confer adjuvant benefits for non-depressed psoriatics who are stress responders. SSRIs, such as fluoxetine, paroxetine, sertraline (Zoloft®), and escitalopram (Lexapro®), are generally safe and better tolerated than other classes of antidepressants.³³

In stress responders, paroxetine may be preferential because of its anti-anxiety effects. It also offers the advantage of having minimal anticholinergic activity and no associated weight gain. Common side-effects include headache, gastrointestinal upset, and sexual dysfunction.33
TCAs, though effective antidepressants, can be lethal in overdose. Side-effects are common and include sedation, weight gain, orthostatic hypotension, and anticholinergic effects. MAOIs may be used to treat patients whose symptoms do not respond to first-line antidepressants (also known as, refractory depression). MAOIs should be prescribed with caution because of their potentially dangerous side-effects (i.e., serotonin syndrome and hypertensive crisis). Common side-effects include orthostatic hypotension, drowsiness, weight gain, sexual dysfunction, dry mouth, and sleep dysfunction.³³

In addition, anti-anxiety medications may be helpful for short-term use in specific stressful situations for stress responders. For instance, alprazolam (Xanax®) is a rapid-acting medication, with both anti-depressant and anti-anxiety effects, that may be beneficial in these situations. Because it has a shorter and more predictable half-life, as compared with other benzodiazepines, there is less risk of accumulation in the body when used over long periods of time. However, alprazolam can be highly sedating and potentially addictive,³⁴ and therefore, treatment should be limited to short-term use on the order of a few weeks to a maximum of a few months.

Conclusion

An extensive number of clinical studies exists supporting stress as an exacerbating factor in psoriasis.^5-12 One problem is that most investigations on stress are generally retrospective, primarily based on patient recall of past events, which may or may not be an entirely reliable measure. However, there are three prospective studies confirming an association between stress and psoriasis.^4,10
In sum, stress appears to be an important precipitating factor in the development and exacerbation of psoriasis. Patients who are identified as stress responders may especially benefit from stress reduction through psychotherapy and/or pharmacotherapy.

References

1. National Psoriasis Foundation website. About psoriasis: statistics. Available at: http:// www.psoriasis.org/netcommunity/learn/about-psoriasis/statistics. Last accessed: December 14, 2010.
2. Devrimci-Ozguven H, Kundakci TN, Kumbasar H, et al. The depression, anxiety, life satisfaction and affective expression levels in psoriasis patients. J Eur Acad Dermatol Venereol 14(4):267-71 (2000 Jul).
3. Koo JY. Psychodermatology: a practical manual for clinicians. Cur Prob Dermatol 6:204-32 (1995).
4. Picardi A, Abeni D. Stressful life events and skin diseases: disentangling evidence from myth. Psychother Psychosom 70(3):118-36 (2001 May-Jun).
5. Gupta MA, Gupta AK, Kirkby S, et al. A psychocutaneous profile of psoriasis patients who are stress reactors. A study of 127 patients. Gen Hosp Psychiatry 11(3):166-73 (1989 May).
6. Rigopoulos D, Gregoriou S, Katrinaki A, et al. Characteristics of psoriasis in Greece: an epidemiological study of a population in a sunny Mediterranean climate. Eur J Dermatol 20(2):189-95 (2010 Mar-Apr).
7. Seville RH. Psoriasis and stress. Br J Dermatol 97(3):297-302 (1977 Sep).
8. Al’Abadie MS, Kent GG, Gawkrodger DJ. The relationship between stress and the onset and exacerbation of psoriasis and other skin conditions. Br J Dermatol 130(2):199-203 (1994 Feb).
9. Zachariae R, Zachariae H, Blomqvist K, et al. Self-reported stress reactivity and psoriasis-related stress of Nordic psoriasis sufferers. J Eur Acad Dermatol Venereol 18(1):27-36 (2004 Jan).
10. Verhoeven EW, Kraaimaat FW, de Jong EM, et al. Individual differences in the effect of daily stressors on psoriasis: a prospective study. Br J Dermatol 161(2):295-9 (2009 Aug).
11. Naldi L, Chatenoud L, Linder D, et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: results from an Italian case-control study. J Invest Dermatol 125(1):61-7 (2005 Jul).
12. Jankovic S, Raznatovic M, Marinkovic J, et al. Risk factors for psoriasis: A case-control study. J Dermatol 36(6):328-34 (2009 Jun).
13. Fortune DG, Richards HL, Kirby B, et al. Psychological distress impairs clearance of psoriasis in patients treated with photochemotherapy. Arch Dermatol 139(6):752-6 (2003 Jun).
14. Arnetz BB, Fjellner B, Eneroth P, et al. Stress and psoriasis: psychoendocrine and metabolic reactions in psoriatic patients during standardized stressor exposure. Psychosom Med 47(6):528-41 (1985 Nov-Dec).
15. Buske-Kirschbaum A, Ebrecht M, Kern S, et al. Endocrine stress responses in TH1-mediated chronic inflammatory skin disease (psoriasis vulgaris)–do they parallel stress-induced endocrine changes in TH2-mediated inflammatory dermatoses (atopic dermatitis)? Psychoneuroendocrinology 31(4):439-46 (2006 May).
16. Evers AW, Verhoeven EW, Kraaimaat FW, et al. How stress gets under the skin: cortisol and stress reactivity in psoriasis. Br J Dermatol 163(5):986-91 (2010 Nov).
17. Richards HL, Ray DW, Kirby B, et al. Response of the hypothalamic-pituitary-adrenal axis to psychological stress in patients with psoriasis. Br J Dermatol 153(6):1114-20 (2005 Dec).
18. Russo PA, Ilchef R, Cooper AJ. Psychiatric morbidity in psoriasis: a review. Australas J Dermatol 45(3):155-9 (2004 Aug).
19. Kimball AB, Jacobson C, Weiss S, et al. The psychosocial burden of psoriasis. Am J Clin Dermatol 6(6):383-92 (2005).
20. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Association (2000).
21. Seng TK, Nee TS. Group therapy: a useful and supportive treatment for psoriasis patients. Int J Dermatol 36(2):110-2 (1997 Feb).
22. Winchell SA, Watts RA. Relaxation therapies in the treatment of psoriasis and possible pathophysiologic mechanisms. J Am Acad Dermatol 18(1 Pt 1):101-4 (1988 Jan).
23. Griffiths CE, Richards HL. Psychological influences in psoriasis. Clin Exp Dermatol 26(4):338-42 (2001 Jun).
24. Price ML, Mottahedin I, Mayo PR. Can psychotherapy help patients with psoriasis? Clin Exp Dermatol 16(2):114-7 (1991 Mar).
25. Kabat-Zinn J, Wheeler E, Light T, et al. Influence of a mindfulness meditation-based stress reduction intervention on rates of skin clearing in patients with moderate to severe psoriasis undergoing phototherapy (UVB) and photochemotherapy (PUVA). Psychosom Med 60(5):625-32 (1998 Sep-Oct).
26. Hardman R, Hopkins EJ, Pye AM, Solomon M, Solomon S. A trial of imipramine in the treatment of psoriasis. J Coll Gen Pract 10(3):315-6 (1965 Nov).
27. Hebel E. [Treatment of psoriasis with imipramine (Tofranil)]. Ugeskr Laeger 128(1):20-1 (1966 Jan 6).
28. Alpsoy E, Ozcan E, Cetin L, et al. Is the efficacy of topical corticosteroid therapy for psoriasis vulgaris enhanced by concurrent moclobemide therapy? A double-blind, placebo-controlled study. J Am Acad Dermatol 38(2 Pt 1):197-200 (1998 Feb).
29. Modell JG, Boyce S, Taylor E, et al. Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study. Psychosom Med 64(5):835-40 (2002 Sep-Oct).
30. Tamer E, Gur G, Polat M, et al. Flare-up of pustular psoriasis with fluoxetine: possibility of a serotoninergic influence? J Dermatolog Treat 20(3):1-3 (2009).
31. Hemlock C, Rosenthal JS, Winston A. Fluoxetine-induced psoriasis. Ann Pharmacother 26(2):211-2 (1992 Feb).
32. Osborne SF, Stafford L, Orr KG. Paroxetine-associated psoriasis. Am J Psychiatry 159(12):2113 (2002 Dec).
33. Katon W, Ciechanowski P. Initial treatment of depression in adults. In: UpToDate. Waltham, MA.
34. DuPont RL, Greene W, Lydiard R. Sedatives and hypnotics: pharmacology and epidemiology. In: UpToDate. Waltham, MA.