Abstract
Inflammatory rheumatic diseases have a long-lasting effect on patients’ physical and psychological functioning, for instance, due to disabling symptoms and unpredictable disease course. Consequently, many patients show adjustment problems such as depressed mood, which in turn can negatively influence their disease outcome. Specific biopsychosocial factors have shown to affect this outcome. For example, daily stress, cognitive-behavioral risk factors such as pain catastrophizing and avoidance, and resilience factors such as optimism and social support influence the quality of life, physical symptoms of pain and fatigue, and inflammatory markers. Psychological interventions tackling these factors can have beneficial effects on physical and psychological functioning. Recent advances in screening for patients at risk, tailored treatment, and eHealth further broaden the efficiency and scope of these interventions while simultaneously optimizing patient empowerment. This chapter describes the biopsychosocial risk and resilience factors related to disease outcome and the possible benefits of psychological treatment strategies in inflammatory rheumatic diseases.
Strong evidence has demonstrated the substantial negative impact of inflammatory rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis on everyday quality of life. Similarly, it has been well-documented that the manner in which patients deal with this chronic stressor affects their long-term physical and psychological functioning, indicating a number of biopsychosocial risk and resilience factors in these patient groups . Tackling these biopsychosocial risk and resilience factors through psychological interventions has shown to have possible benefits for patients with inflammatory rheumatic diseases, with recent advances concerning screening, stepped care, tailoring, and eHealth providing new opportunities for optimizing patient care .
In this chapter, we describe the psychological burden reported by patients with inflammatory rheumatic diseases and the risk and resilience factors related to the quality of life (including physical and psychological functioning) and disease outcome according to prospective and experimental studies in inflammatory rheumatic diseases. In addition, we describe the effects of psychological interventions tackling these factors and outline implications for optimizing patient care in the future including recent advances of screening, stepped care, tailored treatment, and eHealth. Although this review aims to capture various inflammatory rheumatic diseases, it is relevant to mention that most of the studies have been performed in patients with rheumatoid arthritis. Therefore, although studies have shown that quality-of-life impairment and biopsychosocial risk and resilience factors are mostly comparable between diseases , generalizing the findings to all inflammatory rheumatic conditions should be performed with caution. In addition, we use evidence from healthy controls and patients with other chronic somatic conditions in the case of a lack of studies for inflammatory rheumatic diseases.
Psychological burden of inflammatory rheumatic diseases
Inflammatory rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis have a major and long-lasting effect on the quality of life of patients. Their chronic and progressive nature, accompanied by disabling symptoms of pain, stiffness, and fatigue; their need for long-term medication use with potential serious side effects; and their unpredictable disease course lead to patients requiring to adjust to functional disability, to limitations on almost all areas of daily life (such as work, leisure activities, and social and family life), and to a changed and uncertain future perspective . In addition to the effect of the disease on daily life, the pathophysiological disease process itself, with chronic inflammatory activity, may further influence psychological functioning, for example, due to a direct link between inflammatory processes and depressive symptoms .
The level of psychological burden, which can vary from a mild to moderate level of psychological distress to clinical depression and anxiety, differs between diagnostic groups and individual patients and can vary over time . The past decades have shown large improvements in disease activity control of inflammatory rheumatic diseases, as shown by the large decreases in the levels of physical disability, anxiety, and depression . However, the quality of life of patients with inflammatory rheumatic diseases remains considerably lower than that in the general population and is comparable to that in other chronic somatic diseases including cardiovascular conditions and diabetes . Thus, many patients show some level of heightened psychological distress, with a substantial percentage developing clinically relevant levels of distress, such as depression and anxiety, with prevalence rates varying between 10% and 40% depending on the criteria and instruments used (e.g., clinical interviews show lower percentages than screening questionnaires) .
A high psychological burden has been shown to significantly impair the health-related quality of life of patients with inflammatory rheumatic diseases. In addition, it negatively affects disease outcomes including physical disability, remission scores, pharmacological treatment adherence and response, healthcare costs, and mortality . Thus, trying to minimize the level of psychological burden of patients with inflammatory rheumatic diseases is of high clinical relevance, and knowing the factors influencing this burden and their effects on the quality of life and disease outcome will aid in the development and refinement of interventions for these patient groups.
To conclude, the psychological burden of inflammatory rheumatic diseases is substantial, which corresponds to the percentages reported in other chronic somatic conditions, and demands serious attention by the healthcare professionals treating these patients because of its potentially adverse consequences for impaired quality of life and disease outcome.
Risk and resilience factors for quality of life and disease outcome in inflammatory rheumatic diseases
According to the biopsychosocial models of adjustment to disease, the long-term functioning of a person in response to an uncontrollable long-term stressor such as an inflammatory rheumatic disease is determined by a combination of biological, psychological, and social factors. Within such models, both risk factors associated with worse outcomes and resilience factors that protect an individual from potential negative consequences are included. These models mostly consist of a combination of relatively stable personality characteristics, external stressors, and social aspects and a variety of cognitive, emotional, and behavioral risk and resilience factors, which influence the quality of life and disease outcome .
The risk and resilience factors included in the biopsychosocial models as depicted in Fig. 1 could influence the quality of life and disease outcome in inflammatory rheumatic diseases through different routes of possible mediating or moderating effects. As an example of a mediating role, a person high on neuroticism, which is a general tendency to be sensitive and experience high negative affectivity, has a higher chance to cope with stressors in an avoidant manner, which in turn will negatively influence the disease outcome. A moderating effect is, for example, observed in the buffer effect of social support, showing that stressors unfavorably affect disease activity only in the event of low levels of social support. In contrast to irreversible stressors, relatively stable personality characteristics, and elusive social support networks, the cognitive, emotional, and behavioral risk and resilience factors are a focus of psychological interventions and can be changed more easily.
The impact of stressors combined with an individual’s risk and resilience factors on the disease outcome in chronic inflammatory diseases is at least in part explained by psychophysiological responses. Psychological factors such as stressors activate or deactivate, depending on the specific constellation of risk and resilience factors, the stress response systems that show bidirectional relationships with the immune system ( Fig. 2 ). These stress response systems consist of the autonomic nervous system (ANS), which includes the sympathoadrenal medullary (SAM) axis that secretes adrenaline and noradrenaline, and the neuroendocrine system, which includes the hypothalamic–pituitary–adrenal (HPA) axis that secretes cortisol, a major stress regulatory parameter. Because both pathways are connected with the immune system, influencing these pathways through psychological factors may influence disease processes in immune-mediated rheumatic diseases .
In research on adjustment to chronic diseases, including inflammatory rheumatic diseases, the main focus has traditionally been on the risk factors for a poor disease outcome, with far less research on resilience factors that prevent a poor outcome. However, both factors are essential to understand the relative risk of an individual for developing problems or to understand his or her potential for recovery . Knowledge regarding the risk and resilience factors that influence the quality of life and disease outcome in inflammatory rheumatic diseases is crucial for developing screening instruments to identify patients at risk of poor outcome and for developing interventions tailored to specific risk profiles. In the following paragraphs, we provide an overview of the most consistent evidence regarding the predictive role of psychological factors on inflammatory rheumatic diseases, as demonstrated in prospective and experimental studies.
Prospective studies
Within this paragraph, risk and resilience factors that have shown a predictive value for the future physical or psychological functioning of patients with inflammatory rheumatic diseases in prospective studies are summarized.
Some studies have examined the prospective role of personality characteristics in inflammatory rheumatic diseases. These studies confirm the disease-generic finding that high neuroticism, which is characterized by negative affectivity and sensitivity, is a risk factor; in contrast, optimism, which is characterized by a general expectancy for positive outcomes, and extraversion, which is the tendency to be outgoing and energetic, are protective factors for psychological and physical quality of life .
Stressors have been relatively and consistently found to play a role in inflammatory rheumatic diseases, particularly in rheumatoid arthritis. Minor or daily stressors (for example, negative interpersonal events) are associated with more fatigue and pain, elevated immune activity, and disease exacerbations . However, less clear are the results regarding major stressors, such as the death of a loved one. Some studies have indicated major stressors to be associated with the onset of rheumatoid arthritis, although this has been mostly concluded from retrospective studies, whereas other studies showed disease improvement and some studies found no associations . The paradoxical effect of major stressors being associated with disease improvement in some studies has been proposed to be due to the effect of a major versus minor stressor on the psychophysiological stress system activity. For example, major, but not minor, stressors are supposed to lead to increases in cortisol release that dampens immune activity .
Social factors include both the availability and quality of social support by significant others . Good quality social support has shown to protect against psychological distress and increase in physical symptoms . It has, however, also been shown that problematic, unwanted, or stressful relationships lead to increased distress, higher symptom levels, and increased inflammatory activity in rheumatic diseases, thus indicating that the quality of social support is particularly important . Regarding the social aspects within the healthcare context, a satisfactory relationship between the care provider and patient, which, for example, consists of mutual trust and active participation of the patient in treatment and decision making, has been shown to be an important predictor of high patient engagement and well-being in inflammatory rheumatic diseases. High patient engagement or empowerment has been shown to be related to improved treatment adherence, treatment satisfaction, and health-related quality of life .
Cognitive, emotional, and behavioral factors are believed to mediate or moderate the relationship of personality, stressors, and social factors with the quality of life and disease outcome and are frequently a focus of psychological interventions. Cognitive factors that have been found to be related to chronic somatic diseases in general and inflammatory rheumatic diseases in particular include illness perceptions, which are the ideas that patients create about their illness (e.g., disease controllability) , and illness cognitions, which result from an individual’s cognitive evaluation of threatening aspects related to a disease and its consequences (e.g., helplessness and acceptance) . Additional often-studied cognitive factors related to inflammatory rheumatic diseases include catastrophizing, which is the tendency to ruminate about and magnify pain, combined with a feeling of helplessness to manage it and self-efficacy, which is the confidence of a person in his or her ability to handle potential stressors . Emotional factors encompass the general or situation-specific ways that individuals respond emotionally to stressful events (e.g., fear of pain or emotional suppression) . Behavioral factors include the ways in which persons manage situations that they perceive as stressful or as taxing their resources, including general coping strategies or behaviors (e.g., problem-focused coping) and pain-specific behavioral responses (e.g., avoidance) .
Of these factors, perceived helplessness, pain catastrophizing, excessive worrying, fear of pain, and passive avoidance coping have shown relatively consistent prospective associations with more severe psychological distress and physical symptoms and with a larger disease impact on daily life . Some evidence in rheumatic diseases, which corresponds with evidence from other chronic illnesses, has also indicated that specific ways of regulating emotions, including difficulty in identifying and describing emotions (alexithymia) and emotional suppression, are predictive of impaired quality of life and increased self-reported disease activity, whereas other strategies, such as emotional expression, could be associated with improved functioning under specific circumstances . Acceptance and self-efficacy have been shown to generally protect against psychological distress and increase in physical symptoms . More recently, the role of expectancies has become a research topic of particular interest in the area of placebo effects, in which expectancies, for example, with regard to treatment effectiveness, have been shown to be a strong predictor of subsequent outcomes including pain. A recent large observational study in a varied chronic pain sample has shown that the expectancies of patients predict changes in pain intensity and interference .
Experimental studies
Prospective evidence of associations between psychological factors and changes in disease impact of inflammatory rheumatic diseases indicates potential causal relationships of risk and resilience factors for the quality of life and disease outcome in the future. However, causality cannot be ascertained as prospective associations could also be due to factors that are associated with both the risk or resilience factor and the change in quality of life or disease impact. Although the laboratory setting is not a natural environment, which may limit the generalizability of the findings to daily life settings, experimental studies that manipulate a psychological factor and examine its effect on functioning while controlling other key factors enable true causal conclusions . Although not all psychological factors can (easily) be manipulated (e.g., personality characteristics) and not much experimental research has been conducted in patients with inflammatory rheumatic diseases, the following paragraphs will provide the current knowledge base in this or related fields (e.g., pain stimulation in healthy participants or other chronic pain populations).
Personality traits are relatively stable across time and situations, which makes it hard to manipulate them. Nevertheless, recent studies have shown that healthy participants could be trained to become more optimistic, which decreased the amount of pain experienced in response to an experimental pain stimulus and decreased cognitive dysfunction due to pain .
An area in which most experimental evidence has been gathered in inflammatory rheumatic diseases is exposure to experimental stressors, including psychosocial stressors (e.g., public speaking, mental arithmetic), physical stressors (e.g., physical exercise, Valsalva maneuver), and physiological stressors (e.g., hypoglycemia, infusion of corticotropin-releasing hormone). These stressors have shown to induce stress-related SAM, HPA, and immune responses in patients with inflammatory rheumatic diseases, with the strongest effects shown in response to psychosocial stressors . In inflammatory rheumatic diseases, immune responses that are similar to those in experimental stress in healthy individuals have been found; the exceptions are a lower Natural Killer (NK) cell cytotoxicity after stress in patients than in controls, potentially because of chronic immune activation due to the inflammatory disease , and an increased proinflammatory cytokine increase in response to a psychosocial stressor after controlling for elevated baseline levels of proinflammatory cytokines in patients with rheumatoid arthritis . The link between real-life psychosocial stressors and psychophysiological and immune reactivity suggests a potential role of stressors in the maintenance or exacerbation of inflammatory rheumatic diseases, which is in line with the prospective evidence of a link between stressors and disease outcome .
Many studies have also focused on the role of expectancies in determining pain reports in both healthy and clinical populations. As determined from the broad placebo and nocebo literature, expectancies regarding the effectiveness or burden (e.g., side effects) of treatments have a major influence on actual treatment effects and treatment adherence. In healthy participants, it has consistently been found that manipulating expectancies by means of verbal suggestions or conditioning (e.g., through visual cues repeatedly associated with a specific pain stimulus) influences the amount of pain that the participants report in response to an experimental pain stimulus, both decreasing (placebo) and increasing (nocebo) pain . Although less often studied, evidence also suggests the pain-relieving effects of expectancy manipulations in clinical chronic pain populations .
In line with the consistent evidence of a prospective association between pain catastrophizing and disease burden in inflammatory rheumatic diseases, a recent study on both patients with chronic headache and healthy controls has shown that inducing a temporary state of catastrophizing led to increased levels of pain intensity and unpleasantness in response to an experimental pain stimulus. In addition, the level of change in catastrophizing was associated with the change in pain, which is suggestive of a direct pain-enhancing mechanism . Moreover, a reduction in catastrophizing led to reductions in pain report in healthy individuals, which was found to be modulated at the supraspinal level . Finally, providing failure feedback to healthy participants, which may be similar to creating a feeling of helplessness, has been shown to lead to an increase in pain reports .
Risk and resilience factors for quality of life and disease outcome in inflammatory rheumatic diseases
According to the biopsychosocial models of adjustment to disease, the long-term functioning of a person in response to an uncontrollable long-term stressor such as an inflammatory rheumatic disease is determined by a combination of biological, psychological, and social factors. Within such models, both risk factors associated with worse outcomes and resilience factors that protect an individual from potential negative consequences are included. These models mostly consist of a combination of relatively stable personality characteristics, external stressors, and social aspects and a variety of cognitive, emotional, and behavioral risk and resilience factors, which influence the quality of life and disease outcome .
The risk and resilience factors included in the biopsychosocial models as depicted in Fig. 1 could influence the quality of life and disease outcome in inflammatory rheumatic diseases through different routes of possible mediating or moderating effects. As an example of a mediating role, a person high on neuroticism, which is a general tendency to be sensitive and experience high negative affectivity, has a higher chance to cope with stressors in an avoidant manner, which in turn will negatively influence the disease outcome. A moderating effect is, for example, observed in the buffer effect of social support, showing that stressors unfavorably affect disease activity only in the event of low levels of social support. In contrast to irreversible stressors, relatively stable personality characteristics, and elusive social support networks, the cognitive, emotional, and behavioral risk and resilience factors are a focus of psychological interventions and can be changed more easily.
The impact of stressors combined with an individual’s risk and resilience factors on the disease outcome in chronic inflammatory diseases is at least in part explained by psychophysiological responses. Psychological factors such as stressors activate or deactivate, depending on the specific constellation of risk and resilience factors, the stress response systems that show bidirectional relationships with the immune system ( Fig. 2 ). These stress response systems consist of the autonomic nervous system (ANS), which includes the sympathoadrenal medullary (SAM) axis that secretes adrenaline and noradrenaline, and the neuroendocrine system, which includes the hypothalamic–pituitary–adrenal (HPA) axis that secretes cortisol, a major stress regulatory parameter. Because both pathways are connected with the immune system, influencing these pathways through psychological factors may influence disease processes in immune-mediated rheumatic diseases .
In research on adjustment to chronic diseases, including inflammatory rheumatic diseases, the main focus has traditionally been on the risk factors for a poor disease outcome, with far less research on resilience factors that prevent a poor outcome. However, both factors are essential to understand the relative risk of an individual for developing problems or to understand his or her potential for recovery . Knowledge regarding the risk and resilience factors that influence the quality of life and disease outcome in inflammatory rheumatic diseases is crucial for developing screening instruments to identify patients at risk of poor outcome and for developing interventions tailored to specific risk profiles. In the following paragraphs, we provide an overview of the most consistent evidence regarding the predictive role of psychological factors on inflammatory rheumatic diseases, as demonstrated in prospective and experimental studies.
Prospective studies
Within this paragraph, risk and resilience factors that have shown a predictive value for the future physical or psychological functioning of patients with inflammatory rheumatic diseases in prospective studies are summarized.
Some studies have examined the prospective role of personality characteristics in inflammatory rheumatic diseases. These studies confirm the disease-generic finding that high neuroticism, which is characterized by negative affectivity and sensitivity, is a risk factor; in contrast, optimism, which is characterized by a general expectancy for positive outcomes, and extraversion, which is the tendency to be outgoing and energetic, are protective factors for psychological and physical quality of life .
Stressors have been relatively and consistently found to play a role in inflammatory rheumatic diseases, particularly in rheumatoid arthritis. Minor or daily stressors (for example, negative interpersonal events) are associated with more fatigue and pain, elevated immune activity, and disease exacerbations . However, less clear are the results regarding major stressors, such as the death of a loved one. Some studies have indicated major stressors to be associated with the onset of rheumatoid arthritis, although this has been mostly concluded from retrospective studies, whereas other studies showed disease improvement and some studies found no associations . The paradoxical effect of major stressors being associated with disease improvement in some studies has been proposed to be due to the effect of a major versus minor stressor on the psychophysiological stress system activity. For example, major, but not minor, stressors are supposed to lead to increases in cortisol release that dampens immune activity .
Social factors include both the availability and quality of social support by significant others . Good quality social support has shown to protect against psychological distress and increase in physical symptoms . It has, however, also been shown that problematic, unwanted, or stressful relationships lead to increased distress, higher symptom levels, and increased inflammatory activity in rheumatic diseases, thus indicating that the quality of social support is particularly important . Regarding the social aspects within the healthcare context, a satisfactory relationship between the care provider and patient, which, for example, consists of mutual trust and active participation of the patient in treatment and decision making, has been shown to be an important predictor of high patient engagement and well-being in inflammatory rheumatic diseases. High patient engagement or empowerment has been shown to be related to improved treatment adherence, treatment satisfaction, and health-related quality of life .
Cognitive, emotional, and behavioral factors are believed to mediate or moderate the relationship of personality, stressors, and social factors with the quality of life and disease outcome and are frequently a focus of psychological interventions. Cognitive factors that have been found to be related to chronic somatic diseases in general and inflammatory rheumatic diseases in particular include illness perceptions, which are the ideas that patients create about their illness (e.g., disease controllability) , and illness cognitions, which result from an individual’s cognitive evaluation of threatening aspects related to a disease and its consequences (e.g., helplessness and acceptance) . Additional often-studied cognitive factors related to inflammatory rheumatic diseases include catastrophizing, which is the tendency to ruminate about and magnify pain, combined with a feeling of helplessness to manage it and self-efficacy, which is the confidence of a person in his or her ability to handle potential stressors . Emotional factors encompass the general or situation-specific ways that individuals respond emotionally to stressful events (e.g., fear of pain or emotional suppression) . Behavioral factors include the ways in which persons manage situations that they perceive as stressful or as taxing their resources, including general coping strategies or behaviors (e.g., problem-focused coping) and pain-specific behavioral responses (e.g., avoidance) .
Of these factors, perceived helplessness, pain catastrophizing, excessive worrying, fear of pain, and passive avoidance coping have shown relatively consistent prospective associations with more severe psychological distress and physical symptoms and with a larger disease impact on daily life . Some evidence in rheumatic diseases, which corresponds with evidence from other chronic illnesses, has also indicated that specific ways of regulating emotions, including difficulty in identifying and describing emotions (alexithymia) and emotional suppression, are predictive of impaired quality of life and increased self-reported disease activity, whereas other strategies, such as emotional expression, could be associated with improved functioning under specific circumstances . Acceptance and self-efficacy have been shown to generally protect against psychological distress and increase in physical symptoms . More recently, the role of expectancies has become a research topic of particular interest in the area of placebo effects, in which expectancies, for example, with regard to treatment effectiveness, have been shown to be a strong predictor of subsequent outcomes including pain. A recent large observational study in a varied chronic pain sample has shown that the expectancies of patients predict changes in pain intensity and interference .
Experimental studies
Prospective evidence of associations between psychological factors and changes in disease impact of inflammatory rheumatic diseases indicates potential causal relationships of risk and resilience factors for the quality of life and disease outcome in the future. However, causality cannot be ascertained as prospective associations could also be due to factors that are associated with both the risk or resilience factor and the change in quality of life or disease impact. Although the laboratory setting is not a natural environment, which may limit the generalizability of the findings to daily life settings, experimental studies that manipulate a psychological factor and examine its effect on functioning while controlling other key factors enable true causal conclusions . Although not all psychological factors can (easily) be manipulated (e.g., personality characteristics) and not much experimental research has been conducted in patients with inflammatory rheumatic diseases, the following paragraphs will provide the current knowledge base in this or related fields (e.g., pain stimulation in healthy participants or other chronic pain populations).
Personality traits are relatively stable across time and situations, which makes it hard to manipulate them. Nevertheless, recent studies have shown that healthy participants could be trained to become more optimistic, which decreased the amount of pain experienced in response to an experimental pain stimulus and decreased cognitive dysfunction due to pain .
An area in which most experimental evidence has been gathered in inflammatory rheumatic diseases is exposure to experimental stressors, including psychosocial stressors (e.g., public speaking, mental arithmetic), physical stressors (e.g., physical exercise, Valsalva maneuver), and physiological stressors (e.g., hypoglycemia, infusion of corticotropin-releasing hormone). These stressors have shown to induce stress-related SAM, HPA, and immune responses in patients with inflammatory rheumatic diseases, with the strongest effects shown in response to psychosocial stressors . In inflammatory rheumatic diseases, immune responses that are similar to those in experimental stress in healthy individuals have been found; the exceptions are a lower Natural Killer (NK) cell cytotoxicity after stress in patients than in controls, potentially because of chronic immune activation due to the inflammatory disease , and an increased proinflammatory cytokine increase in response to a psychosocial stressor after controlling for elevated baseline levels of proinflammatory cytokines in patients with rheumatoid arthritis . The link between real-life psychosocial stressors and psychophysiological and immune reactivity suggests a potential role of stressors in the maintenance or exacerbation of inflammatory rheumatic diseases, which is in line with the prospective evidence of a link between stressors and disease outcome .
Many studies have also focused on the role of expectancies in determining pain reports in both healthy and clinical populations. As determined from the broad placebo and nocebo literature, expectancies regarding the effectiveness or burden (e.g., side effects) of treatments have a major influence on actual treatment effects and treatment adherence. In healthy participants, it has consistently been found that manipulating expectancies by means of verbal suggestions or conditioning (e.g., through visual cues repeatedly associated with a specific pain stimulus) influences the amount of pain that the participants report in response to an experimental pain stimulus, both decreasing (placebo) and increasing (nocebo) pain . Although less often studied, evidence also suggests the pain-relieving effects of expectancy manipulations in clinical chronic pain populations .
In line with the consistent evidence of a prospective association between pain catastrophizing and disease burden in inflammatory rheumatic diseases, a recent study on both patients with chronic headache and healthy controls has shown that inducing a temporary state of catastrophizing led to increased levels of pain intensity and unpleasantness in response to an experimental pain stimulus. In addition, the level of change in catastrophizing was associated with the change in pain, which is suggestive of a direct pain-enhancing mechanism . Moreover, a reduction in catastrophizing led to reductions in pain report in healthy individuals, which was found to be modulated at the supraspinal level . Finally, providing failure feedback to healthy participants, which may be similar to creating a feeling of helplessness, has been shown to lead to an increase in pain reports .
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