Free Online CME

Cleveland Clinic Basic and Clinical Immunology for the Busy Clinician Online Series

The Immunologic Basis of Wellness for Patients with Immune Mediated Inflammatory Disorders

Leonard H Calabrese, DO
M. Elaine Husni, MD, MPH

Immune mediated inflammatory diseases (IMIDs) are a broad family of diseases of the immune system characterized by inflammation mediated by common pathways involving cytokines (i.e. TNF, IL1, IL6 others). IMIDs are diverse in nature and clinical manifestations but can often be treated with similar medications. Prominent among IMIDs are relatively common diseases such as rheumatoid arthritis (RA) spondyloarthritis, psoriasis, inflammatory bowel disease and others. A further conceptual view suggests that many extremely common diseases which previously were viewed as degenerative in nature now should be viewed as inflammatory, greatly expanding this construct. Such candidate diseases now being treated with many of the same anti-inflammatory agents and strategies include cardiovascular disease including heart disease and stroke, dementia, diabetes, and others. Collectively it has been estimated that there are 50 million people in the United States with some form of autoimmune disease.

Over the past two decades remarkable progress has been made in treating these diseases leading to improved clinical outcomes and prolonged survival. Much of these gains are related to the impact of biologic therapeutics manufactured via recombinant technology. These drugs include a growing list of injectable monoclonal proteins designed to target select cytokines and immune competent cells. More recently small molecules, including kinase inhibitors, have been developed which also appear remarkably potent at controlling numerous IMIDs, offering oral options as well. Simply stated, biologics and immunomodulatory therapies have raised the bar in the treatment of IMIDs. However, these drugs, while potent, have significant untoward adverse effects and are costly. Furthermore, no biologic or immunomodulatory agent has cured any IMID and afflicted patients continue to bear significant burdens of disease which profoundly affect their quality of life. Thus new approaches are still needed for this population of patients.

Patients with IMIDs may want to be healthy but disease is incompatible with heath. Patients with IMIDs can, however, achieve wellness - which refers to diverse and interconnected dimensions including physical, mental, and social wellbeing that extend beyond the traditional definition of health. Growing evidence suggests that wellness can be achieved through individual choices and activities including avoiding harm (e.g. excess of alcohol, drugs, smoking, etc.) as well as engaging in exercise, healthy eating, and achieving optimal mental and spiritual health.

Over the past two decades there is growing evidence that chronic low grade inflammation is a driver of many non-communicable diseases (e.g. diabetes, obesity, metabolic syndrome, fatty liver, cardiovascular disease, and immune mediated disease) (1). Many of these drivers of inflammation relate to behavior (i.e. diet, sleep, exercise, stress) and are of particular importance for patients with immune mediated diseases. Unfortunately there are no drugs, either conventional or biologic, that can result in wellness and clinicians treating IMID patients are challenged as how to promote wellness in their practice. Accordingly, programs to address behaviors are urgently needed. At present there is a significant body of data suggesting that pro-wellness interventions are logical adjuncts for the treatment of IMIDs. For example in the setting of rheumatoid arthritis, a disease afflicting 2 million Americans, it has been demonstrated that pro-wellness activities such as healthy eating of an diet that would be viewed as anti-inflammatory can meaningfully reduce the risk of the disease(1) (2). Consider that infections are a co-morbidity in all patients with IMIDs and a particular concern in RA and there are data in the general population that clearly demonstrate reduced risk of respiratory illness with moderate exercise (3). This is particularly acute for even those without underlying immune mediated disorders in the current pandemic of COVID-19 (4). The presence of intercurrent mood abnormalities in RA have been correlated with poorer quality of life, increased pain, and fatigue. Modalities such as mindfulness training in the form of Mind Body Stress Reduction (MBSR) and other techniques may be potentially helpful as they have positive effects on reducing pain and fatigue in many disorders including fibromyalgia, low back pain, and RA (1, 5). Finally, sleep is an important dimension of wellness and lack of quality sleep may be a confounder in IMIDs as well(6).

While few would argue with the goals of implementing interventions to promote wellness for patients with immunologic disease, numerous obstacles exist including a lack of declarative knowledge among providers on the relative benefits of such interventions and a sense that the field of wellness research is a soft science. In addition there is a lack of procedural knowledge among providers dealing with complex IMID patients on how to incorporate such education, monitoring, and assessment in the context of a busy clinical practice.

Toward these ends, we have been developing an online platform of organized wellness training for patients with immune mediated diseases based on the theory of empowerment through knowledge and awareness that human behavior affects immune function. Using a series of videos and allied messaging techniques and guided by a trained coach the participant will be guided in assessing, modifying and monitoring four wellness domains (mindfulness and sleep behavioral training, dietary advice, and exercise guidance). Pre and posttest assessment of quality of life and disease activity are planned for each subject. Our hypothesis is that immune wellness behavioral training plus standard of care for common immune diseases (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis to start) will improve outcomes. The program is called “Immune Strength” and is a product of Cleveland Clinic interdepartmental development including the RJ Fasenmyer Center for Clinical Immunology, Wellness, and Preventive Medicine.

Intervention

Obstacles

Significant obstacles exist for implementation of efforts to promote wellness in patients with IMIDs. A recent study designed to explore roadblocks to implement behavioral change for exercise identified several (7). These included lacking knowledge and confidence on what to do or where to refer, access to pragmatic interventions, understating norms and language of behavioral change for patients, and a belief that it is beyond the scope of their practice. An effective program for wellness must address each of these domains from the provider’s perspective.

An effective intervention for wellness for patients with IMIDs will overcome patient related obstacles as well. Among these are providing both context and motivation supporting patients’ efforts and their belief that their effort will make a difference for their wellbeing. Having access to modalities that are practical with achievable goals is also important. Finally incorporating techniques to increase adherence such as allowing patients to self-assess their needs and track their progress are important in designing an intervention.

Annotated Bibliography

  1. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-32.
  2. A world class review of the scientific basis of chronic low grade inflammation as a driver of common non-communicable diseases including diabetes, heart disease, stroke, obesity and others. A review of biobehavioral interventions is also discussed.

  3. Sparks JA, Barbhaiya M, Tedeschi SK, Leatherwood CL, Tabung FK, Speyer CB, et al. Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women. Clin Rheumatol. 2019;38(1):243-50.
  4. The longest and largest epidemiologic study to examine the effects of lifestyle performed in over 30,000 nurses followed for over 30 years showing that a prudent diet versus the standard western diet is protective for incident RA.

  5. Nieman DC, Wentz LM. The compelling link between physical activity and the body's defense system. J Sport Health Sci. 2019;8(3):201-17.
  6. Nieman DC. Coronavirus disease-2019: A tocsin to our aging, unfit, corpulent, and immunodeficient society. J Sport Health Sci. 2020;9(4):293-301.
  7. These two studies demonstrate the body of work spanning preclinincal models to human training experiments with careful epidemiologic investigations. This has demonstrated that regular moderate exercise protects against common respiratory infections and enhances immune function.

  8. Black DS, Slavich GM. Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Ann N Y Acad Sci. 2016;1373(1):13-24.
  9. Irwin MR. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol. 2019;19(11):702-15.
  10. These two studies summarize the new field of social genomics which implies that our behavior has downstream effects at the molecular level via epigenomic reprogramming. They also explore the importance of sleep hygiene in the area and the potential for mind-body techniques to influence gene programming.