Bridging the Physical and the Mental: The Effects of Chronic Stress on Rheumatoid Arthritis
Evan Seker
Illustrations by Elizabeth Catizone
Susan, a 25-year-old digital media manager, spends hours every week typing on her laptop. After a while, her hands begin to experience an unfamiliar ache, affecting her performance at work; tasks that once took Susan 30 minutes to complete now take over an hour. In her quest to identify the problem, Susan consults different doctors and takes their recommendations for various pain medications. After months of visits to several specialists, a blood test finally provides a diagnosis. Susan has rheumatoid arthritis, an autoimmune disorder that causes her immune system to attack her joints.
Let’s follow Susan through a day in her life with her new diagnosis. Getting out of bed takes longer than before, so now she sets an earlier alarm. Susan takes her coffee with prescribed painkillers and sits at her desk, which has been modified to accommodate her new physical limitations. Today is particularly stressful because she needs to submit an important report to her boss, and the stress Susan experiences causes her symptoms to flare up and she feels her joint pain more acutely. Despite her best efforts to manage her symptoms, the condition continues to worsen and Susan feels helpless.
Susan comes across an internet article on the link between chronic stress and certain autoimmune disorders, including rheumatoid arthritis. She is initially skeptical as ‘cure-alls’ are exceedingly rare and unlikely to be promising, but all the article asks her to do is meditate for 30 minutes a day, have something to look forward to at the end of each week, and take steps to make her life more enjoyable. With these suggestions in mind, Susan puts forth a significant effort towards living mindfully, and in a month, her symptoms have decreased and her pain has improved. While managing stress did not cure Susan’s rheumatoid arthritis, it did help reduce her painful symptoms. But, how are rheumatoid arthritis and stress connected?
On the Defensive
Whether it be submitting an assignment at the last minute or rushing to catch a train, we have all experienced stress. While uncomfortable, short-term stress is a normal part of the human experience and can be beneficial, boosting our focus and enhancing our physical performance [1, 2]. In a state of stress, our body goes into overdrive to address a challenge. Typically, when the challenge — or the stressor — is removed, the stress subsides and our body returns to normal [2]. While short-term stress is adaptive, long-term or chronic stress is maladaptive and has several negative effects on the body [3, 4]. When someone experiences long-term stress, their body fails to return to baseline after the stressor disappears [1, 5]. Chronic stress can affect a variety of organs: including the heart, gut, and brain [6, 7, 8]. The effects of chronic stress can also have ramifications on body systems, most notably the immune system.
The immune system protects the body by coordinating attacks against possible threats, which include harmful external substances known as pathogens as well as the body’s own damaged cells [9]. When the body identifies a possible pathogen or experiences tissue damage, such as from a paper cut, the immune system dispatches small messenger molecules called cytokines [10]. Cytokine release triggers inflammation, during which blood vessels widen to increase blood flow and send an influx of specialized immune cells to the site of infection [11, 12]. The inflammatory response — one of the body’s first lines of self-defense against pathogens — is a quick and effective component of immunity that is heavily regulated by the brain [13, 14, 15].
Typically, the brain modulates the immune system in response to environmental factors, like stress [15, 16, 17]. The stress response is initiated in the hypothalamus, a brain region responsible for regulating bodily functions such as temperature control, our sense of hunger, and hormone release [18, 19]. The hypothalamus sends a chemical signal to the pituitary gland, located at the base of the brain, which in turn signals the adrenal glands that are located above the kidneys [18]. The signal cascade culminates in the release of the hormone cortisol from the adrenal glands [18, 20, 21]. Cortisol inhibits the release of proinflammatory cytokines — much like a skilled referee prevents players from committing fouls — and contributes to the initial downregulation of the inflammatory response [20, 21]. The suppression of immune processes allows for the reallocation of energy toward other, more urgent bodily functions, such as fighting off a threat or fleeing from it [20, 22]. This short-term stress response is not only typical, but necessary for survival [2]. However, chronic stress decreases the efficacy of cortisol, leading to dysregulation of the immune system, which can worsen pre-existing symptoms of immune-related disorders [3, 21, 23, 24].
When the Defensive Becomes the Offensive
Normally, the immune system distinguishes the familiar — that which belongs to the body — from the foreign — that which comes from outside the body [24, 25]. The ability to recognize the body’s tissues and spare them from an immune attack is known as self-tolerance, and is a crucial component of the immune response [26]. Sometimes, the highly coordinated self-tolerance response goes awry, and the immune system’s ability to recognize its own immune cells fails [24]. When self-tolerance is lost, autoimmune disorders arise [24]. Autoimmune disorders are a type of disease in which the immune system misidentifies the body’s own cells as foreign entities, prompting the attack of healthy cells, tissues, and organs [26, 27]. There is no single cause of an autoimmune disease that has been isolated; rather, autoimmune diseases develop as a result of both genetic and environmental factors [28].
Rheumatoid arthritis (RA) is one autoimmune disease that involves the loss of self-tolerance in the joints [25]. In RA, the immune system erroneously identifies the joints as foreign and mounts an attack against them [29]. The misrecognition of benign joint proteins as foreign stimulates local inflammation, leading to pain, swelling, and tissue damage in the area [30]. These attacks weaken joint tissue, impacting mobility and fine motor skills such as typing, writing, and finger-gripping [31]. The immune system then recognizes the resulting tissue damage and prompts an inflammatory response to bring more immune cells to the damaged site [32]. In doing so, a devastating positive feedback loop is created as the immune system continues to target the damaged area. Therefore, the inflammation in Susan’s joints remains elevated, and the condition worsens. [32]. Over time, the constant barrage of immune attacks one experiences can lead to irreversible disability [33, 34].
A Joint Effort You Don’t Want
Chronic stress can negatively affect the prognosis and induce an earlier onset of RA by continuously stimulating the release of cortisol [35, 36, 20]. Over time, the body develops resistance to cortisol and no longer responds as strongly to its signals, diminishing its immunosuppressive effects [37, 20]. Now, cortisol is like a referee who has lost control of its players. With cortisol’s ability to regulate the immune system dampened, immune activators are able to promote rampant inflammation [20, 37, 38]. Unchecked inflammation accelerates the degradation of joint tissues, thereby exacerbating RA symptoms, much like a game of soccer without a referee in which players would become more erratic and fouls more frequent [35, 39, 20, 38]. Chronic stress enhances immune dysfunction, significantly impacting the prognosis of people living with RA [2]. Both RA and stress aggravate each other in a vicious circle [40, 37, 3]. Not only is chronic stress a risk factor for the development of RA, but it drastically increases the severity of symptoms individuals with RA experience [36, 41, 42, 40]. In turn, RA contributes to the onset and magnitude of chronic stress, resulting in a poorer quality of life and increased pain level for people with RA [40, 43]. Given the influential role stress plays on exacerbating RA symptoms and rate of progression, treatments aimed at mitigating chronic stress have the potential to improve prognoses for individuals living with RA [44].
DMARDs and Downward Dog
Several medical treatments known as disease-modifying antirheumatic drugs (DMARDs) are already available to slow RA progression [33, 45]. DMARDs are a type of immunosuppressive medication and come in two forms: conventional and biologic [45]. The difference between the two lies in their specificity. While conventional DMARDs suppress the entire immune system, biologic DMARDs target specific elements of the immune response for a more precise therapeutic treatment. Suppressing the immune system in RA blunts attacks against one’s joints [45]. Unfortunately, treatment with DMARDs tends to have adverse side effects, most prominently a higher risk of infections due to suppression of the immune system [46]. A promising addition to RA treatment plans involves stress-relieving therapies like meditation, targeted breathing, and yoga [47, 48, 1]. Intentional lifestyle change that promotes stress relief — such as hanging out with friends, adopting a more positive mindset, or simply asking others for help with problems — can also improve the quality of life of individuals living with RA by providing relief from the stress they experience [2, 3, 47, 49]. Though stress reduction does not cure RA, it can be used in conjunction with medical treatment in a disease management plan to reduce side effects and unwanted drug interactions that individuals with RA experience during treatment [3, 50].
Medicate, Meditate, Alleviate, Remediate
Months later, Susan is successfully managing life with RA. After employing a combination of medical treatment and lifestyle changes, her symptoms are becoming less frequent and noticeable, and the physical limitations she once had are gradually fading. Although RA is incurable, there is hope for individuals living with the condition to mitigate the impact of the disease on their lives. Overall, since chronic stress exacerbates effects of RA, efforts to reduce chronic stress may prove successful in alleviating debilitating symptoms that people with RA experience [3, 47, 50, 51]. By taking steps to reduce chronic stress, people living with RA may be able to live happier, more comfortable lives [47, 49].
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