Module 1: Autoimmunity: The Challenge

Having reached 5% worldwide1 prevalence, Autoimmune disease represents a growing challenge to the medical community and general population. More than 100 autoimmune diseases have been identified2, and many have experienced rapid growth in recent decades.3 The risk of developing an autoimmune disease in the United States has surpassed that of both cardiovascular disease and cancer1, and its economic burden has nearly doubled that of cancer,4 underscoring the need for deeper understanding of the mechanisms by which the body misrecognizes and attacks its own tissues. Typically chronic and requiring lifelong treatment,5 autoimmune diseases can affect every organ system in the body, and their physical, functional, social, mental and emotional influences on both patients and their families are unduly devastating.

While what is known about autoimmune disease is vastly eclipsed by what remains unknown, several key observations can ground our understanding and frame our ongoing investigation. First, recent decades have witnessed a sharp increase in the incidence of autoimmune disease in industrialized nations while at the same time, infectious diseases have been on the decline.5 The rise in autoimmune disease incidence is paralleled by improved socioeconomic status and movement towards a Westernized lifestyle, characterized by psychosocial stress and a pervasive emphasis on economic productivity, enhanced sanitation and hygiene practices, a diet rich in sugar, fat and often fast food, low levels of physical activity and increased levels of smoking, alcohol consumption and exposure to chemical pollutants, xenobiotics, and other toxicants.3,5,6,7,8 Taken together, these factors stress the body in ways to which it is not evolutionarily accustomed; whereas the collective focus on productivity and economic gain creates undue psychological stress, poor diet and inadequate exercise lead to obesity and altered gut microbial profiles, predisposing towards autoimmunity;5 and while associations between cigarette smoking, alcohol and increased disease risk are well established for many conditions – autoimmune or otherwise, new insights about the inflammatory and immune-stimulating effects of pollutants, xenobiotics, overmedication, and toxicants on the body are continually being uncovered.

Born out of this shift towards industrialization and its attendant improvements in sanitation and negative lifestyle impacts is the hygiene hypothesis – the idea that the reduced infectious disease burden resulting from improved health and sanitation practices has had the unintended consequence limiting the immune system’s exposure to pathogens that might yield protective or otherwise beneficial effects and ultimately, allowed the immune system to shift its focus towards endogenous constituents.3,7 Second, while genetic predisposition is implicated in autoimmunity, genetic profiles in affected countries have remained largely unchanged during this period in which autoimmunity has peaked; this, coupled with the observation that those who migrate from a developing nation with low autoimmune prevalence to an industrialized nation with high autoimmune prevalence assume the adopted country’s rates of autoimmune incidence, sometimes as soon as within one generation,3 indicates that the above-mentioned environmental factors may overshadow genetic factors as triggers of autoimmunity.3,5

The manifestations of autoimmunity are widely variant, with marked clinical differences across autoimmune disease types and between individuals carrying the same autoimmune disease diagnosis.1 Many of the autoimmune diseases with the highest rates of incidence increase in recent years have been rheumatological, endocrine and gastrointestinal in nature, while autoimmune diseases affecting the nervous system are also becoming increasingly common.3,9 Despite the extensive clinical variance, some common features are consistent with the spectrum of autoimmune diseases, chief among them inflammation, stress, pain and gut dysbiosis.7,8 In light of the fact that autoimmunity tends to preferentially affect women,7 with some sources estimating female predominance at 80%,1,9 it is not uncommon for reproductive hormonal imbalance to accompany many autoimmune patients’ clinical presentations.

While the westernization of societies experiencing an uptick in autoimmune prevalence has afforded better economic status, the lifestyle shifts that have accompanied this evolution are highly inflammatory, leading to dysregulation of the immune system through maladaptive cytokine (or perhaps, ‘signaling’?) responses that favor the development and preserve the maintenance of autoimmune disease. As will be discussed in subsequent sections, autoimmunity is in essence a self-perpetuating process: once the weight of triggering insults becomes sufficient to break immune tolerance, the immune system activates numerous processes to maintain this state of self-attack.

Further complicating the clinical picture of autoimmunity is the tendency of symptoms to relapse and remit throughout the disease course, often in accordance with psychosocial stressors related to work or family life and/or hormonal shifts such as pregnancy or menopause. Many symptoms may be vague and resemble common ailments of modern life, such as fatigue, joint aches, and digestive distress; this is particularly common in early stages of disease. Because aberrations in immune function that lead to autoimmunity may occur years before clinical symptoms manifest,7 pursuing diagnosis and treatment at the earliest signs of illness is critical to the avoidance of further unchecked damage. The often elusive and shape-shifting nature of autoimmune symptoms makes these conditions difficult to diagnose, and many go unrecognized for months if not years, at which point the physiologic burden may have grown to an extent that prohibits the patient from living a fully-functional life. What’s more, many autoimmune diseases have clinical presentations that don’t fit neatly into a singular category or specialty, requiring patients to seek medical attention from multiple healthcare practitioners. Though having many proverbial hands on deck seems, in theory, a thorough treatment approach, the highly segmented nature of the current medical paradigm does little to promote communication and collaboration between providers in a way that would foster comprehensive patient-focused care and therefore, yield better clinical outcomes. The onus of communicating to a team of providers may be trickled down to the patient, whose health literacy may not be sufficient to provide an adequate representation of findings and feedback to each provider, and whose emotional vulnerability as a chronically ill patient may further impede the capacity to communicate effectively. In the absence of a collaborative team approach to autoimmune patient care, a clear and comprehensive picture of the patient’s progress cannot be obtained, further distancing the patient from the intended objective of care – an optimal treatment outcome in the form of disease remission, symptom alleviation, and improved function and well being. This is not to malign the medical community or place blame, but rather to highlight the context in which certain patient populations may become particularly vulnerable within the current healthcare construct, autoimmune patients among them.

Implicit within the discussion of patient care is the topic of treatment, namely pharmaceutical therapy. Historically, autoimmunity has been regarded as the result of aberrant signaling leading to inappropriate activation of self-reactive cells and accordingly, this view has been the guiding principle behind immunosuppressive therapies. More recently, autoimmunity has come to be seen as a bi-directional phenomenon composed of two requisite defects: the above-mentioned alteration in signaling leading the immune system to target host tissue and a defect in the immune system’s ability to regulate self-reactive cells.10 To that end, research into novel therapies that address autoimmune diseases from multiple angles is ongoing. The traditional model of immune suppression may have the unsavory side effect of leaving the patient vulnerable to opportunistic infection, as its effects are systemic instead of targeted to the affected organ, tissue or source of the disease. Further, this approach is accompanied by risk of side effects and drug toxicity, further compounding disease states. Some treatments, such as co-stimulatory blockade, show promise in dampening the immune response by deactivating self-reactive cells but ultimately fall short as their effects are broad, leading to systemic immune suppression, and target only naive immune cells and not those that have been previously activated.10 With reduced levels and/or impaired function of Treg cells characterizing many autoimmune conditions, therapy focused on activating and expanding Treg cell populations seems a viable treatment avenue, however the efficacy of this in vitro process has not readily translated to in vivo success, and, alarmingly, Treg cells have demonstrated a capacity to convert to pathogenic T cell subsets that may contribute to disease states.10 Antigen administration, perhaps best known in the context of allergy treatment, entails exposing the patient to a disease-provoking agent – an antigen – in calculated doses in order to desensitize the immune system and alter its response threshold. That the present research and understanding of which antigens contribute to specific autoimmune diseases is limited serves as an obstacle for this particular therapeutic option, as does the potential for disease exacerbation it confers.10 IL-2 therapy, which focuses on promoting the immunosuppressive and anti-inflammatory properties of the cytokine IL-2, has shown efficacy in the treatment of Myasthenia Gravis, Type 1 Diabetes, and animal models of Multiple Sclerosis. Its broad targeting of the immune system may leave patients vulnerable to infections, however, and its capacity to stimulate various types of immune cells creates the potential for activation of pathogenic immune cells and therefore, disease exacerbation.10

It is common practice to prescribe non steroidal anti-inflammatory pain medications for relief of pain in the joints or elsewhere in the body; while these over-the-counter medications have moderate analgesic effect, their impact is short lived, requiring frequent dosing. Chronic usage of such medications poses the problem of increased risk of bleeding, ulcer, heartburn, high blood pressure as well as liver and kidney problems. Medications with stronger analgesic effect, including opioids and some off-label anti-seizure medications, are attractive options owing to their improved pain control, but heighten the risk of sedation, dependence/addiction, changes in appetite, and changes in mood, among others.

This sampling of therapeutic interventions is neither exhaustive nor reflective of the many novel treatment approaches currently in the nascent stages of development and is therefore not intended to represent the entirety of autoimmune treatment options, but rather to illustrate the challenges of treating complex conditions such as autoimmune diseases. Pharmacologic therapy is undoubtedly a life-preserving component of an autoimmune disease patient’s treatment regimen; that patients often need to take multiple medications, and experience side effects that may either require further pharmacologic therapy and/or negatively impact general function, however, invokes a need for supportive and complementary therapies that attenuate both symptoms of disease and side effects of medication, and promote functional capacity and quality of life.

Looking beyond treatment objectives, efficacy and side effects, an easily overlooked aspect of autoimmune disease management is that it typically targets the physiological aspects of a patient’s illness to the exclusion of it’s mental, emotional and spiritual effects. While the physical manifestations of autoimmune disease represent a very real and significant dimension of the patient, the mental and emotional dimensions are equally involved and relevant to the overall presentation. Put otherwise, a patient deserves to be seen, respected and treated as a whole person, a composite of physical, mental, emotional and spiritual elements; treatment that distills the patient’s experience to physical symptoms alone will therefore be limited in affecting a global and lasting impact on the patient’s symptoms, function and well being. Furthermore, the burden of autoimmune disease is inherently stressful, and may significantly impact mental and emotional health. Chronically ill patients have been shown to have greater levels of psychological stress,11 and are twice as likely to suffer from psychiatric disorders such as depression and anxiety than healthy individuals free of chronic disease.12  With more severe disease presentations curbing the patient’s capacity to work, partake in meaningful social relationships and incurring significant financial burden, the stress load may be further inflated, making the mental and emotional aspects of a patient’s disease ever-more worthy of attention.

No medical intervention is perfect, and no therapy, no matter how well substantiated by research and clinical practice, can wholly serve an entire patient population’s needs. To that end, it is crucial to identify therapeutic modalities that support and complement ongoing allopathic care.

At present, research is continually yielding new insights into contributing factors, mechanisms and potential abortive, palliative and preventive treatment approaches. An exciting and promising time, no doubt, however it is still a time in which there are many more questions than answers, and in order to best serve the individuals who suffer from autoimmune conditions, accommodations must be made to compensate for any unmet needs. To that end, this paper examines the role of complementary therapy in supplementing ongoing medical treatment as a means of improving both quantitative and qualitative treatment outcomes through a patient-centered approach. Specifically, acupuncture will be highlighted as a complementary treatment modality, and a detailed discussion of the mechanisms by which this time-tested therapy exerts its effects as well as its demonstrated and potential efficacy in alleviating some of the common features of autoimmunity will be provided. This paper does not posit that acupuncture could or should play a singular role in the treatment of autoimmune conditions but rather substantiates the need for change as it relates to the treatment of autoimmunity at all points along the disease continuum, from diagnosis, to the treatment of flare and remission states, to prevention. With the burden of autoimmunity exceeding the healthcare system’s capacity to affect appreciable meaningful and lasting change in the lives of autoimmune disease patients, the time to explore new avenues has come.