Rethinking Chronic Disease
At some level, I have always felt something was amiss in our approach to Western medical practice. While the goal of restoring homeostasis in people with chronic disease remains aspirational, even with the newest therapies, it raises the question: is this due to the shortcomings of our technologies, or is it a consequence of Western Medicine’s reductionist and deterministic approach to human biology?
We previously discussed how our reductionist and deterministic interpretation of reality appears so ingrained that it continues to persist in the scientific process despite the overwhelming evidence showing the interaction between physiological, psychological, and socio-environmental factors in humans disease.
This becomes even more relevant when considering the landscape of treatment options and the clinical outcomes they provide for patients with chronic, inflammatory, and autoimmune diseases. These conditions are a striking example of how disruptions to biological networks—like the immune and nervous systems—contribute to the chronic nature of these diseases, highlighting the limitations of our current approaches. These diseases, which were relatively rare at the beginning of the 20th Century, saw a sharp rise in prevalence during the 1980s and 1990s. They now affect over 50 million people in the United States alone.
The evidence is clear that complex, bidirectional relationships exist between autoimmunity, mental health disorders, nutrition, socioeconomic status, lifestyle, and stress exposure. These are some of the most impactful determinants of health. Yet, in clinical studies and medical practice, the evaluation of these patients is often limited to the effect of immunosuppression on disease-specific outcomes in isolation rather than in the context of quality of life, overall well-being, and mental outcomes.
One critical observation from decades of clinical research across autoimmune conditions is that immunological therapies tend to yield near-identical response patterns across clinical trials regardless of the compound, its potency, or its mechanism of action.
On average, only 10-20% of patients achieve complete remission. While most achieve partial control at best, up to one-third experience minimal or no improvement. Rather than raising the possibility that our approach may be limited or partial at best or that we are ignoring the broader framework of human health, we seem more content accepting the idea of a “therapeutic ceiling” or “plateau of response” and resign to the fact that most treatments provide marginal benefit for a large proportion of the patient population.
In practice, this means that the best possible outcome for most patients with autoimmune disease is partial disease control until new treatment options become available.
While it is true that newer options, particularly cell-based therapies, seem to offer more promise even in patients with refractory disease, they still do not fulfill the goal of restoring homeostasis.
This ‘therapeutic ceiling’ highlights the limitations of targeting immune pathways in isolation. For instance, while biologics targeting key drivers of immune response such as TNF-alpha, have revolutionized the treatment for autoimmune conditions like rheumatoid arthritis, they still leave a significant proportion of patients with suboptimal or no response.
To move beyond partial disease control, we must also address the broader system’s interplay with non-immunological factors such as nutrition, emotional health, and gut health. These factors influence immune regulation, stress resilience, and overall system balance, highlighting their pivotal role in achieving sustainable health outcomes.
Consider the immune system: In a resting, homeostatic state, it functions as a complex, adaptive, non-linear, and non-hierarchical network with multiple feedback loops and interactions with other systems like the environment, the microbiome, and the nervous system. When homeostasis is disrupted by infection, injury, or trauma, the immune system reorganizes into a more hierarchical structure to manage inflammation and repair damage. This reorganization is crucial for immediate survival, aiming to restore balance and return to a state of tolerance. However, if the inflammatory process becomes self-sustaining, the immune system may lose its ability to regulate itself or adequately distinguish between self and non-self, leading to autoimmune and chronic inflammatory diseases. In a sense, the system becomes "stuck" in a defensive posture, unable to recalibrate to its baseline state.
Similarly, the neurological system responds to perceived threats by activating stress responses such as the "fight or flight" mechanism, designed to restore balance quickly. If stressors persist or significant trauma occurs, these responses can become chronic, leading to a range of physical and neuropsychiatric conditions characterized by altered stress responses, a loss of tolerance, and an altered sense of self. These changes can profoundly impact how individuals perceive and interact with reality, leading to a state where once-helpful mechanisms become entrenched, altering how individuals experience and respond to their environment.
For instance, chronic stress has been linked to heightened inflammation and disrupted sleep patterns, which further entrench maladaptive cycles and exacerbate both physical and mental health issues.
This reinforces the need to move beyond symptom management to address the systemic patterns that perpetuate disease.
There is a striking parallel between these examples in physiological and psychological domains. In both, highly adaptive responses to external events can become self-sustaining, leading to a prolonged loss of homeostasis. Whether the immune system is trapped in a cycle of chronic inflammation or the nervous system is stuck in a continual state of stress, the core issue remains the same—a failure to restore balance.
The similarities and interdependence of the immune and nervous systems, along with the growing evidence of the connection between autoimmune and inflammatory disorders, suggest a potential shared pathogenesis for these diseases.
Understanding these biological dynamics is essential as we examine the broader determinants of chronic disease and how they influence our ability to return to health. In the next post, we will explore the role of trauma as a fundamental disruptor of homeostasis, driving maladaptive patterns across the mind and body. Join me as we continue this journey toward a more integrative vision of human health and rediscover what it means to heal.