Influences of stress and nutrition

Psoriasis sufferers have an increased risk of affective disorders. Accordingly, they should be asked about depression, anxiety, and problematic coping with illness such as social avoidance behavior and alcohol abuse. Training courses on daily living, nutrition and skin care exist and have proven useful. Physicians and patients should be aware of the increased risk for cardiovascular disease and diabetes mellitus. Lifestyle and diet (low-calorie, preferably Mediterranean) should be adjusted. The importance of obesity and smoking as proven risk factors and also their sometimes negative effects on therapy should be explained to the patient. Appropriate lifestyle changes should be supported. Psoriatic patients should be asked about symptoms of gluten sensitivity and tested for gluten antibodies if positive. Complex and expensive therapies could be saved by a gluten-free diet.

The treatment of psoriasis is primarily guided by immunomodulatory topical and systemic therapeutics as well as phototherapy. Many people are not aware that psoriasis, as a multifactorial disease, can also be favorably influenced by lifestyle measures. Since not all sufferers respond the same way to the various measures, there is no specific psoriasis lifestyle or diet. Those affected must do much more to identify the influencing factors that are relevant to them and become aware of the possibilities for exerting their own influence. The factors of stress, psychological comorbidities, diet, obesity, and smoking are discussed below.

Psoriasis – current knowledge and treatment standards

Psoriasis is a systemic inflammatory skin disease with a prevalence of approximately 2-3% in the general population. The etiology is not fully understood, but a multifactorial genesis is assumed with genetic, environmental, and behavioral factors, which most likely also explains the variability in prevalences between different countries (USA 0.9%, Norway 8.5%) [1]. The course can fluctuate widely and be associated with a reduction in quality of life similar to that of cardiovascular disease and certain cancers [2].

In recent years, new potent but also cost-intensive immunosuppressants, the biologics, have become increasingly important in psoriasis treatment. This is associated with increasing treatment costs (25,000-35,000 CHF per year), especially considering the chronicity of this disease. It is therefore all the more important to pay attention to unrecognized etiologic factors that may favorably influence therapy or prevent exacerbations.

In order to therapeutically address the multifactorial genesis, a multimodal approach should be adopted. Genetic predisposition per se cannot be changed, of course – but in recent years it has become increasingly clear that lifestyle and diet affect gene activation via epigenetic mechanisms and influence inflammatory processes [3]. At the same time, the increased risk of comorbidities such as cardiovascular disease and diabetes mellitus can be reduced as a result.

Psyche and stress

Skin diseases are associated with considerably increased comorbidity for mental illness.

The extent of these associations was again highlighted in a European multicenter cross-sectional study published in 2014. In thirteen states, 3635 persons with skin disease and 1359 controls were surveyed regarding depression, anxiety disorder, and suicidal ideation. Psoriasis represented the largest group (17.4%). Overall, the disturbance patterns mentioned occurred almost twice as frequently in the skin patients (29%) as in the control group (16%). Depression occurred more than twice as often, and anxiety disorders or suicidal thoughts about one and a half times as often as in the control group. The psoriasis subgroup in particular showed high values for these three disorders (13.8%, 22.7%, and 17.3%, respectively) [4]. The psychological condition can be caused by the disease symptoms themselves, the experience of stigmatization, social fears or a negative body image (Fig. 1) . On the other hand, psychological stress, i.e. emotional stress (referred to in the following as “stress”), can also trigger psoriasis attacks or worsen the course of the disease.

Stress: Generally, emotional stress is observed as a trigger of various dermatological diseases such as atopic dermatitis, acne vulgaris and chronic urticaria. Studies also show a consistent association between stress and clinical expression in psoriasis [5]. In fact, a large proportion of psoriasis sufferers identify stress as the main cause of exacerbations, ahead of infections, trauma, medications, and diet [6]. However, disease severity and treatment outcome can also be negatively affected by stress [7,8]. Conversely, psychological interventions are often associated with clinical improvement [9,10]. However, in accordance with the multifactorial genesis, this does not apply to all psoriasis sufferers. A distinction is made here between so-called “stress responders” and “stress non-responders” [11].

Between 39% and 61% of psoriasis sufferers are “stress responders” [12]. The studies classified stress into three categories: major stressful life events, psychological or personality difficulties, and lack of social support.

Stress is always a subjective experience and arises when a demand (from the environment or from oneself) or its assessment exceeds the available resources (e.g. social support, personality style, solution strategies). (Fig. 2). In a recent cross-sectional study, “stress responders” were found to have significantly elevated scores for depression and personality traits such as anxiety, distrust, and lack of assertiveness [13]. Thus, it appears to be a more psychologically vulnerable population. Few prospective studies on stress and psoriasis exist [7,14,15] and the exact relationships and mechanisms are not fully understood.

However, this subgroup exhibits different stress biomarkers, as evidenced by attenuated cortisol release after acute stress [16]. Several experimental studies have demonstrated an attenuated hypothalamic-pituitary-adrenal axis response and an enhanced sympathetic catecholaminergic response to stress in psoriasis sufferers, corresponding to lower cortisol and higher catecholamine release during stress [16–19]. These changes attenuate the endogenous anti-inflammatory effect, which increases the release of proinflammatory cytokines, activates skin mast cells, and impairs skin barrier function [19]. Thus, a similar mechanism as in the flare-up of psoriasis after steroid withdrawal.

Therapy: In view of the high comorbidity of affective disorders, psychotherapeutic, educational and stress reduction measures are recommended. However, the evidence base for specific interventions is heterogeneous and larger randomized controlled trials are lacking. However, it is important to remember that psychological interventions are more difficult to standardize than pharmacological interventions because they are dependent on the user and on participant preference and compliance. Among the best-studied methods are cognitive behavioral therapy, Jakobson progressive muscle relaxation, and mindfulness meditation [12]. Central and independent of the method is the induction of a state of relaxation (“relaxation response”) to counteract the stress state. Antagonistic physiological-hormonal mechanisms have been described for this (Fig. 3). This mechanism can also be supported by endurance sports and sufficient sleep.

The gold standard is considered to be cognitive behavioral therapy in a multidisciplinary group setting over six weeks, which according to studies is associated with improvement in physical, psychological, and quality-of-life parameters [9]. This approach is all the more important because illness experience has been identified as the strongest predictor of stress and disability [20].

Influences of nutritional factors

In recent years, it has become increasingly clear that numerous dietary components exert an inflammation-modulating effect on chronic low-grade inflammation [21]. Especially for the Mediterranean diet with its high proportion of fruits, vegetables, nuts and fish, this has been epidemiologically proven [22]. This effect is attributed to the numerous phytonutrients, fibers and omega-3 fatty acids. In contrast, refined carbohydrates and various fats tend to be pro-inflammatory [23]. Although these are low-threshold effects, over the years the effect accumulates not insignificantly. If the diet is strongly altered in favor of a low-carbohydrate so-called “ketogenic diet,” more potent effects on inflammation are possible, as has been shown for neurological diseases, cancer, and acne [24]. Likewise, this effect is supported by the intake of marine omega-3 fatty acids (fatty sea fish) [25]. However, there is little conclusive evidence for specific diets in psoriasis. This is probably due to individual variability and research methodological difficulties. Thus, individual dietary components such as gluten, fatty acids, vitamin D, and antioxidant supplements have been increasingly studied. It has been shown that a diet rich in fresh fruits and vegetables is associated with a lower risk of psoriasis [26]. Among supplements, omega-3 fatty acids were found to be most likely to benefit, although the data are inconclusive. An overview of the study situation is provided in Table 1.

Fatty acids: Polyunsaturated fatty acids, which include omega-6 and omega-3 fatty acids, are significantly involved in inflammatory processes in addition to their hormonal and immunological functions. Elevated levels of arachidonic acid, an omega-6 fatty acid, are found in the skin of psoriatic plaques. Arachidonic acid is converted by the enzyme phospholipase A2 to leukotriene B4, a potent proinflammatory mediator. The same enzyme converts EPA, an omega-3 fatty acid, into leukotriene B5 and prostaglandin-E3, which have lower inflammatory activity. In this process, omega-3 and omega-6 fatty acids compete for the same enzyme. Thus, the presence of the fatty acid substrate is critical for the more or less inflammatory metabolites. Increased levels of omega-3 fatty acids are thought to have an anti-inflammatory effect and improve psoriasis symptoms [27]. However, studies on omega-3 fatty acid supplementation in psoriasis have not shown any conclusive effects. This is not surprising since serum baseline values were not measured and different supplement doses and bioavailabilities existed. Accordingly, the strongest effects were shown by lipid infusion treatments.

Gluten: Psoriasis sufferers have a higher prevalence of other autoimmune diseases such as celiac disease, Crohn’s disease, and ulcerative colitis. Studies suggest common genetic and inflammatory processes [28]. In a large American cohort study [29], psoriasis sufferers (n=25 341) had a 2.2-fold increased risk for the presence of celiac disease and a 2.4-fold increased risk for gluten sensitivity (pos. anti-gliadin antibodies, no enteropathy). Accordingly, a gluten-free diet was shown to significantly reduce psoriasis severity in individual case reports [30,31] and two clinical trials of AGA-positive patients [32,33]. This suggests an association between gluten sensitivity and psoriasis, especially since evidence of increased intestinal permeability has been found in psoriasis [34].

Weight loss: visceral obesity is associated with a proinflammatory state via secretion of cytokines such as TNF-α and IL-6 from adipocytes. In several studies, obesity was associated with increased psoriasis incidence and severity as well as attenuated therapeutic effect of certain drugs [35]. Furthermore, the cytokines IL-17 and IL-23, which are relevant to psoriasis, were elevated in obese women but not in lean women [36]. In a large English cohort study of 75 395 psoriasis patients, obesity was recognized as a risk factor for developing psoriatic arthritis [37]. Several prospective controlled studies of weight reduction using calorie-restricted diets in obesity have demonstrated an effect on psoriasis severity and arthritis that is additive to dermatologic treatment [35]. Interestingly, a reduction in circulating inflammatory cytokines was observed in obese individuals as a result of the calorie-restricted diet [38]. Also very illustrative are the effects of bariatric surgery, which produced considerable improvement in psoriatic activity in several case studies [39,40].

Psoriasis sufferers have an increased cardiovascular risk and also an increased risk of diabetes [41]. The cause is thought to be reduced insulin sensitivity due to systemic inflammation. Similarly, it is itself an independent cardiovascular risk factor [42]. It is therefore all the more important that psoriasis sufferers are aware of this risk and take care of their lifestyle accordingly.

Smoking and alcohol

An analysis of several large cohort studies (Nurses Health Study, Health Professionals’ Follow-up Study) confirmed smoking as an independent risk factor with gradually increased incidence risk depending on the number of pack-years and duration of cigarette use. The relative incidence risk for 5-24 cigarettes daily was even twice as high (RR 2.04) [43]. A prospective study in patients with palmoplantar pustulosis even demonstrated clinical improvement after smoking cessation compared with smoking persistence [44].

Overconsumption of alcohol is also common in psoriasis patients and correlates with disease severity and treatment response [45]. However, a causal relationship could not be confirmed. This behavior is just as conceivable as a reaction to the burden of disease.

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