Chronic pain is one of the most disabling aspects of autoimmune disease, yet too often it is misunderstood, misdiagnosed, or dismissed entirely — especially for women, who make up the vast majority of those affected. Misdiagnosis and bias compound the biological complexity of conditions like lupus and Sjögren’s disease, delaying care until damage is irreversible. The result is unnecessary suffering and years of lost health that could be prevented with better tools, better training, and better science. Tackling the root causes of autoimmune pain means addressing sex differences, hidden biases, and neglected biology to deliver real, lasting relief.
Introduction: When Pain Speaks but Medicine Doesn’t Listen
For millions of people living with autoimmune diseases, pain is not a side effect — it is often the first sign that something is wrong and the daily reminder that something remains unsolved. Yet for far too many, especially women, this pain is a story told but rarely heard. From unexplained fatigue and joint pain to burning nerve sensations and deep muscle aches, autoimmune pain defies simple explanation or easy measurement. It shifts, recedes, and returns without clear warning, slipping through the cracks of a medical system built to treat straightforward problems with clear-cut tests.
This mismatch between patient experience and medical response is one reason why chronic pain remains one of the most disabling yet neglected aspects of autoimmune disease. Despite decades of progress in immunology and diagnostics, the hidden layers of pain and their real biological drivers are still poorly understood and too often dismissed as stress, anxiety, or exaggeration when they appear in women. Pain is complex, but bias compounds that complexity into avoidable suffering.
Addressing this challenge begins with recognizing that complexity and bias are two sides of the same problem. Solving one without tackling the other leaves patients in the same cycle: misunderstood symptoms, delayed answers, and ineffective relief. If the goal is to truly change the outlook for autoimmune patients, the path forward must acknowledge pain for what it is: not just a symptom to suppress, but a signal demanding to be decoded and respected at its source.
The Complexity of Autoimmune Pain: Why the Signals Are So Hard to Read
Pain in autoimmune disease is rarely straightforward. It manifests as a shifting landscape of signals that can arise from multiple biological sources at once, change intensity from day to day, and defy simple explanations. For many patients, this pain is chronic and layered: inflammation in joints and tissues creates one kind of pain, while damaged nerves spark burning or tingling sensations, and the central nervous system itself can become hypersensitive, amplifying pain signals long after active inflammation subsides.1,2 This is especially true in conditions like lupus and Sjögren’s disease, where inflammatory flares coexist with non-inflammatory syndromes such as fibromyalgia, adding a further layer of complexity to what patients feel and how it is understood.
Even when inflammation appears under control through immunosuppressive treatment, pain may persist or even worsen, leaving both patients and clinicians searching for explanations that may not be apparent on lab reports or scans. The result is often a cycle of trial and error: new medications are added, and dosages are adjusted, but the root cause remains elusive.
This ambiguity is made worse by how easily autoimmune symptoms overlap with other conditions. The fatigue, cognitive fog, muscle aches, and generalized pain experienced by autoimmune patients can resemble depression, anxiety, fibromyalgia, or chronic fatigue syndrome, and misdiagnosis is common, often delaying appropriate care for years.3,4 Without a single, definitive test for most autoimmune diseases, diagnosis depends on a careful process of reporting and attempting pattern recognition across unquantifiable complaints.5
For many companies, this level of biological complexity might seem like an obstacle too large to tackle. At Fab Biopharma, it is the reality that defines the work. By acknowledging that pain in autoimmune disease is not caused by one factor alone but by intersecting pathways that shift over time, Fab aims to design therapies that do more than mask symptoms; they address the tangled biology at the core of these misunderstood conditions.
Gender Biases That Deepen the Diagnostic Gap
The biological complexity that makes autoimmune pain so difficult to decode is only part of the story. Equally influential is the reality that how patients describe their pain and how healthcare systems interpret it is shaped by gender bias at every step. For decades, research has shown that women’s reports of pain are more likely to be discounted, downplayed, or reframed as signs of emotional distress rather than legitimate physical disease.6–8 This dynamic is so common that the term medical gaslighting has emerged as a way to describe the repeated experience of having real symptoms explained away as stress, anxiety, or overreaction.
The consequences of this bias show up in treatment patterns that are remarkably consistent around the world. Studies find that when men and women present with similar levels of pain, men are more likely to receive aggressive pain relief, including stronger medications or referrals to pain specialists, while women are more likely to be offered sedatives, antidepressants, or counseling.5,7 For women living with undiagnosed autoimmune diseases, being steered toward mental health explanations can mean years on the wrong treatment path while underlying inflammation, nerve damage, or tissue destruction quietly progresses.
The diagnostic gap is particularly wide when the symptoms themselves don’t fit into discrete checklists. Many autoimmune conditions start with vague, overlapping complaints: deep fatigue, muscle aches, brain fog, intermittent and scattered joint pain. For women, these are exactly the symptoms most likely to be dismissed as psychosomatic, illustrated by countless patient stories of being told to “manage stress” or “get more sleep” instead of receiving further testing.9 Even when more obvious signs appear — skin rashes, organ involvement, positive antibody tests — the early window for timely intervention may have already closed.
This bias is embedded not only in interactions between physicians and patients but also in the design of the research meant to fix it. Women have long been underrepresented in clinical trials for pain and autoimmune treatments, leading to therapies that are often optimized for a default male patient, whose immune system, hormone profile, and pain pathways may differ in significant ways from those of most patients (i.e., women) living with these conditions.10 When studies do include women, they typically aggregate data from both sexes rather than investigating men and women separately, masking patterns that could guide more personalized approaches to dosing, safety, and long-term effectiveness.
In addition to this widespread gender bias, racial and ethnic disparities can further widen diagnostic gaps. Women of color often face a double burden: they are more likely to have their pain minimized or misdiagnosed and less likely to have access to specialists who understand the nuances of complex autoimmune presentations.11 These intersecting biases not only delay care but distort the data that future treatments rely on, creating a feedback loop where those who need relief most are left with the least evidence-based options.
This problem reflects a fundamental failure of both ethics and science. Bias not only distorts patient care in real time; it also skews the clinical evidence base that shapes research pipelines and drug development. For autoimmune diseases where pain is both a core symptom and a critical clue, dismissing or misinterpreting that pain means leaving some of the most important signals out of the picture entirely. Breaking this cycle requires a commitment to confront bias head-on: designing trials that capture real-world diversity, analyzing data by sex, and developing therapies that reflect the true biology and lived reality of the people who will rely on them.
The Cost of Misdiagnosis and Delay
While the complexities of autoimmune pain and the biases that distort its recognition each pose their own challenges, together they create a perfect storm of missed opportunities for timely diagnosis. For many people living with autoimmune diseases, this storm translates into years of uncertainty and untreated progression. Studies estimate that the average time from first symptoms to formal diagnosis for many autoimmune conditions ranges from four to seven years, but it can be even longer.2,3
For lupus, often called “the great imitator,” this delay is especially well-documented. Because lupus can affect nearly any organ system and its symptoms (e.g., fatigue, joint pain, rashes, brain fog) overlap with so many other conditions, patients are frequently told they have depression, chronic fatigue syndrome, anxiety, rheumatoid arthritis, or, worse, that their complaints are simply manifestations of hypochondria.2 Each wrong turn in this diagnostic maze adds more months or years in which the disease can quietly cause inflammation that scars organs and damages joints or nerves in ways that cannot be undone.
Sjögren’s disease presents its own version of this challenge. Often striking women in midlife, it is still routinely mistaken for menopause or side effects of stress or medications, because its hallmark symptoms (dry eyes and mouth, chronic fatigue, vague joint pain) are easily dismissed as lifestyle-related inconveniences.4 Meanwhile, the deeper damage Sjögren’s can cause, including neuropathic pain and small fiber nerve damage, is frequently overlooked because dryness dominates the conversation, overshadowing the complex pain patients live with every day.
When diagnosis lags, inflammation continues unchecked, leading to permanent harm to organs, nerves, and tissues that cannot be fully reversed with medication once the damage has been done. Joint destruction, kidney impairment, peripheral nerve damage, and severe fatigue that become part of daily life are just some of the outcomes that delayed recognition makes more likely. This physical toll is compounded by a psychological one: patients often begin to internalize the doubt they encounter in exam rooms, questioning their own experiences, wondering if their pain really is “all in their head,” as they are often told.12,13
Beyond the human cost of diagnostic delays, the economic impact is enormous. Patients endure repeated specialist visits, multiple rounds of inconclusive testing, ineffective treatments aimed at misdiagnosed conditions, and time lost to disability that could have been prevented with earlier intervention. The cycle drains not just personal savings but public health resources as well.
However, despite these considerable barriers, a quiet shift is underway. Faced with dismissal and confusion, more patients, especially women, are turning to online patient communities, peer-led forums, and patient advocacy groups to share experiences, exchange information, and seek out second or even third medical opinions when initial answers fall short.4,6 These networks are helping patients find the language to articulate complex symptoms and are driving a cultural shift toward self-advocacy that is becoming increasingly essential in navigating conditions that medicine still struggles to define and detect early.
For companies like Fab Biopharma, this is a call to action as much as it is a reality check. Every year shaved off the diagnostic timeline means a greater chance to intervene before damage takes root. Every barrier to an accurate diagnosis removed by better science — clearer biomarkers, more nuanced understanding of overlapping conditions, and therapies that target multiple pathways of pain and inflammation — is a step closer to giving patients back the time, function, and confidence that misdiagnosis too often steals.
When Pain Masks More Than One Disease
Autoimmune diseases often don’t appear alone. Many patients live with more than one autoimmune condition, either as a primary and secondary diagnosis or as overlapping diseases that co-develop and influence each other. Sjögren’s disease and lupus, for example, frequently present together, and their shared symptoms — joint pain, fatigue, neuropathy, cognitive fog — can blur the boundaries between conditions.
Chronic pain often dominates the diagnostic picture, especially when it is severe, persistent, and poorly explained. This can shift the focus of medical evaluations toward managing pain rather than uncovering additional disease processes. As a result, key features of co-morbid autoimmune diseases, such as glandular dysfunction, rashes, internal organ involvement, or immune dysregulation, may be overlooked or misattributed.
The masking effect extends beyond symptoms. Pain can also obscure physiological markers, complicate interpretation of lab results, and interact with medications in ways that cloud diagnosis. For instance, corticosteroids prescribed for pain or inflammation may temporarily suppress antibody activity, altering disease signals and delaying confirmation of a second autoimmune diagnosis.
Complicating matters further, some patients may have coexisting conditions that are not traditionally autoimmune but share overlapping features — and may, in fact, have emerging immunologic components. Ehlers-Danlos syndrome (EDS), a group of hereditary connective tissue disorders marked by collagen abnormalities, is increasingly recognized as one such condition. While EDS is classically associated with joint instability, chronic musculoskeletal pain, fatigue, and dysautonomia, recent findings suggest potential immune involvement and comorbidity with autoimmune disorders, such as lupus and Sjögren’s.
Pain is a shared hallmark of both EDS and autoimmune disease, but the mechanisms are often viewed as distinct: mechanical pain from joint laxity in EDS versus inflammation-driven or neuropathic pain in autoimmune conditions. However, growing evidence points to shared pathways, including neuroinflammation and central sensitization, that may blur these boundaries and suggest a role for immune modulation in at least some subsets of EDS-related pain.
This evolving understanding has major implications for diagnosis and treatment. Pain in EDS may be misattributed to autoimmune flares, or vice versa, leading to incomplete care. Conversely, patients may miss opportunities for immune-targeted interventions if their symptoms are assumed to be purely mechanical. Recognizing the complex interplay between connective tissue integrity, immune signaling, and pain perception reinforces the need for comprehensive, system-wide evaluation and for treating pain not just as a symptom but as a signal that may illuminate deeper biological connections.
Pain: The Neglected Dimension of Autoimmunity
For many living with autoimmune diseases, pain is far more than an inconvenience or a secondary complaint; it is one of the most disabling, life-defining aspects of the condition. But for decades, pain in autoimmunity has been treated as a symptom to be tolerated or masked rather than as a biological process that demands its own targeted solutions.5,11 This oversight is especially costly because pain is often the main reason patients first seek medical help and the primary barrier to maintaining work, relationships, and basic quality of life when treatment falls short.
In lupus, pain can take multiple forms at once, each with its own mechanism but overlapping impact. Inflammatory pain in the joints and muscles (arthralgia and myalgia) is common during flares, creating swelling, stiffness, and mobility loss. But many lupus patients also experience non-inflammatory pain syndromes, especially fibromyalgia, which affects up to half of all people living with lupus. This creates central sensitization, where the nervous system becomes hypersensitive and amplifies pain signals beyond the original injury or inflammation.2 Validating and treating this type of pain is notoriously difficult because it may not correlate with visible signs of inflammation.
Sjögren’s disease adds another overlooked layer to the pain conversation. While dryness dominates its clinical profile, many patients live with persistent joint pain, muscle discomfort, and, crucially, neuropathic pain — tingling, burning, or electric shock–like sensations caused by damage to small peripheral nerve fibers.1 Small fiber neuropathy is common but often unrecognized in Sjögren’s, in part because the tests needed to confirm it are invasive, costly, or simply not offered as standard practice, leaving patients with pain that goes unexplained and undertreated for years.
Despite the massive burden it places on daily life, pain in women, especially chronic, hard-to-measure pain, receives little research attention and funding. Even though women experience chronic pain conditions at higher rates than men, they have historically been left out of pain studies or grouped into analyses that fail to ask why their pain may arise, persist, or respond to treatment differently.7 The result is new therapies that may focus narrowly on inflammation control while ignoring the underlying mechanisms that sustain pain long after inflammation subsides.
Clearly, this gap is not acceptable. Truly meaningful relief for autoimmune diseases cannot be achieved by silencing inflammation alone if patients remain trapped in cycles of unrelenting pain. Addressing pain biology, whether it is driven by nerves, immune cells, or the brain’s own processing of signals, is just as important as controlling the immune system that set it in motion. By targeting the overlooked drivers of pain alongside the immune pathways that spark it, thoughtful drug developers can help rewrite the story for patients who have been told for too long that pain is just something they must learn to live with.
The Role of Emerging Pain Targets: A Glimpse at What’s Next
While pain has long been treated as an unavoidable side effect of autoimmune disease, a new wave of research and development in pain management shows that this does not have to be the case forever. In recent years, the search for safer, more targeted pain relief has led to promising advances in non-opioid pain therapeutics, particularly for acute and post-surgical pain. Companies are making real strides with selective inhibitors and modulators of ion channels like Nav1.8 and Nav1.7, which help transmit pain signals along nerves, as well as targets like TRPV1 and P2X7 that regulate how pain is processed and amplified in the body’s inflammatory pathways.
These innovations are urgently needed to tackle the opioid crisis — a crisis that has its own gender dimension. Roughly one in four patients prescribed opioids after surgery still uses them months later, with women facing an even higher risk of long-term dependency because chronic pain conditions are more prevalent and often undertreated in women.5 More selective pain targets could block pain transmission without the sedation, addiction, or broad immune suppression that opioids bring.
Despite this clear momentum, much of the focus remains on short-term or localized pain, such as pain after surgery or injury. Meanwhile, the same biological pathways — the ion channels and receptors that transmit, amplify, or blunt pain signals — are also at the heart of chronic inflammatory and neuropathic pain, the very types of pain that define conditions like lupus and Sjögren’s. These pathways are simply underexplored when it comes to autoimmunity.
Research must also investigate whether these emerging pain targets function the same way in women as in men. Research increasingly shows that pain pathways can differ by sex, from how ion channels behave under hormonal influence to how nerve sensitivity is modulated by estrogen and other factors.5,10 If new pain treatments are developed without considering these differences, the gender gap in pain care may persist even as new technologies promise more precise control.
The frontier of non-opioid pain science should not stop at the recovery room door but must bridge learnings from post-surgical pain innovation to the neglected realm of chronic autoimmune pain. Exploring how ion channel modulators and other targeted approaches could be adapted to the persistent, multi-layered pain that autoimmune patients experience and how sex differences should inform dosing and design can help close the gap between cutting-edge science and the real pain patients still carry every day.
Closing the Gap
The complexity and bias that so often define autoimmune pain are not immovable barriers but problems that can be addressed by science and evidence-based and ethically sound policy. For patients who have spent years navigating misdiagnosis, dismissal, and unrelenting pain, what’s needed now is not just incremental improvement but a deliberate effort to rethink how we diagnose, study, and treat these diseases at their root.
First, better diagnostic tools are essential. Advances in immunology, molecular biology, and digital health hold real promise for creating biomarkers that go beyond confirming inflammation to help detect the subtle patterns that distinguish inflammatory from neuropathic or sensitization-driven pain and even indicate how pain might behave across hormonal cycles or life stages.1 Such tools could shorten the diagnostic timeline dramatically and allow physicians to intervene before irreversible damage sets in.
The design of clinical trials must change to reflect the reality that sex and gender shape how pain and immune disease appear, progress, and respond to treatment. Including women in trials is not enough if results are averaged together in ways that mask critical differences. Analyzing and publishing sex-disaggregated data should be standard practice across indications beyond autoimmune disease, allowing researchers and physicians to see what works, for whom, and why.10
At the same time, tackling bias requires not only better tools and data but a cultural shift in how future clinicians are trained. Medical schools and continuing education programs must equip physicians to recognize that “typical” presentation often means “male” by default, and that the subtle, shifting nature of autoimmune pain in women is not a reason to dismiss it but rather a reason to look closer and ask better questions.6
On the therapeutic front, new pain treatments must move beyond simply dampening symptoms. The next generation of biologics and targeted therapies needs to address the real biology that drives chronic inflammatory and neuropathic pain to quiet the flares at the source, calm overactive nerve pathways, and reset the circuits that keep pain signals firing even after inflammation has resolved.
For Fab Biopharma, these priorities are not theoretical. They define the path forward: developing therapies that do not treat patients as statistical averages but as people with complex, sex-informed biology and real, daily pain that deserves more than temporary relief. The goal is to close the long-standing gaps between symptom and science, pain and proof and help ensure that the patients who have borne the greatest burden finally see real solutions built with their realities in mind.
Conclusion: Complexity Is Not an Excuse
Autoimmune pain may be biologically complex and diagnostically challenging, but the suffering it causes is neither mysterious nor inevitable. The cycles of misdiagnosis, dismissal, and inadequate treatment that so many patients endure can be broken if science and healthcare systems are willing to fully see the realities these patients live with every day. That means accepting that gender differences matter, that fluctuating symptoms do not make pain less real, and that chronic pain is a condition in its own right that demands dedicated solutions, not just temporary suppression.
Fab Biopharma’s commitment is rooted in this recognition. By pairing advances in immunology and molecular design with a clear focus on closing the gender gap in research and care, Fab aims to develop therapies that address not only inflammation but also the deeper pain pathways and diagnostic blind spots that have held progress back for too long.
The message is simple but urgent: listen to patients, decode the complexity rather than dismiss it, and deliver relief that does more than mute symptoms for a moment — relief that lasts, because it works at the level where pain begins.
References
1. Singh, Gurmit. “Is chronic pain as an autoimmune disease?” Canadian Journal of Pain. 6: 2175205 (2022).
2. Sloan, Melanie, et al. “‘I still can’t forget those words’: mixed methods study of the persisting impact on patients reporting psychosomatic and psychiatric misdiagnoses.” Rheumatology. 64: 3842–3853 (2025).
3. “The Most Difficult Autoimmune Diseases to Diagnose.” AMN Healthcare. 26 Sep. 2024.
4. Rauf, Don. “Autoimmune Diseases Misdiagnosed as ‘All in Your Head’ Can Have Long-Lasting Impact.” Everyday Health. 3 Mar. 2025.
5. Clark, J David, et al. “Autoinflammatory and autoimmune contributions to complex regional pain syndrome.” Mol. Pain. 14: 1744806918799127 (2018).
6. “Gaslighting in women’s health: No, it’s not just in your head.” Katz Institute for Women’s Health. Accessed 10 Jul. 2025.
7. “Women and pain: Disparities in experience and treatment.” Harvard Health Publishing. 9 Oct. 2017.
8. Lacagnina, Michael J, et al. “Autoimmune regulation of chronic pain.” Pain Rep. 6: e905 (2021).
9. Notarantonio, Lucy. “Woman With Autoimmune Disease Shares Common Symptoms She Ignored.” Newsweek. 9 Nov. 2024.
10. Leclair, Valérie, Harmony Tsui, and Marie Hudson. “Pain in autoimmune inflammatory myopathies: a scoping review.” RMD Open. 9: e002591 (2023).
11. Flanagan, Eoin P, et al. “Autoimmune Encephalitis Misdiagnosis in Adults.” JAMA Neurol. 80: 30–39 (2022).
12. Trachman, Susan B. “The Impact of Misdiagnosed Autoimmune Disorders.” Psychology Today. 10 Mar. 2025.
13. Meredith, Sheena. “Autoimmune Disease Misdiagnoses Can Cause Long-Term Harm.” Medscape News UK. 6 Mar. 2025.