Is Fibromyalgia an autoimmune disease?

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Written By Dr. Marcus Yu Bin Pai

MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.

Fibromyalgia: A Chronic Pain Syndrome

Fibromyalgia is a chronic pain syndrome diagnosed by the presence of widespread body pain. Patients typically have diffuse chronic pain and almost always have secondary symptoms of comorbidities, such as fatigue, memory problems, sleep and mood disorders.

The physical exam is typically normal, but there is often diffuse painful hypersensitivity, which can be assessed by counting the number of tender points on the body.

Fibromyalgia is currently a disorder that is part of a spectrum of syndromes that do not have a precise classification. Patients with fibromyalgia share symptoms with other autoimmune diseases, including myalgias and arthralgias.

Advances in Understanding Fibromyalgia

Fortunately, scientific knowledge of fibromyalgia has come a long way since the days when influential physicians viewed fibromyalgia as a “virtual disease” and patients with fibromyalgia were considered “normal people whose individual personality traits and vulnerability predispose them to lead a life of somatization.”

Significant progress has been made in understanding fibromyalgia in the past decade. One long-standing but neglected observation is the inflammation of small nerve fibers, which supports the proposal to consider fibromyalgia as a chronic neuropathic pain syndrome with a probable autoimmune origin.

Furthermore, the association of hyperalgesia, loss of small peripheral nerve fibers, and local precipitation of antibodies has been described in mice that were injected with serum from patients diagnosed with fibromyalgia.

Is Fibromyalgia an Autoimmune Disease?

So, is “everything autoimmune until proven otherwise”?… The answer is a resounding no. In the case of fibromyalgia, although inflammatory, infectious, and autoimmune disorders can be considered as probable inducers of fibromyalgia, as with other diseases of ill-defined origin, there is still very little data to confirm this thesis.

However, fibromyalgia is an extremely important syndrome for doctors and scientists to be aware of. Patients should be taken very seriously and receive the best possible care.

We must recognize that new information proposes a fundamental line of investigation: Is fibromyalgia an autoimmune disease? Should patients with suspected fibromyalgia be tested immunologically? Is it valid to look for evidence that points to aberrant responses due to innate or acquired errors of the immune system that explain their clinical condition in patients with fibromyalgia?

In our clinical practice, we are not surprised to find patients previously qualified as fibromyalgia and/or seronegative autoimmune diseases, showing positive markers for autoinflammatory conditions or subclinical chronic infections, associated with innate or acquired errors of the immune system, susceptible to immune treatment.

Fibromyalgia and Autoimmunity: The Evidence

Autoantibodies and Immune Markers

One of the key pieces of evidence that has fueled the autoimmune hypothesis in fibromyalgia is the presence of certain autoantibodies in some patients. These autoantibodies are proteins produced by the immune system that mistakenly target and attack the body’s own tissues or molecules.

Anti-68/48 kD and Anti-45 kD Antibodies

Studies have reported the presence of anti-68/48 kD and anti-45 kD antibodies in subsets of fibromyalgia patients. These autoantibodies have been associated with specific clinical manifestations, such as hypersomnia, cognitive disorders, and psychiatric symptoms. The anti-68/48 kD antibodies, in particular, have been linked to fibromyalgia and chronic fatigue syndrome patients presenting with sleep disturbances and cognitive impairment.

Antinuclear Antibodies (ANA) and Thyroid Antibodies

Antinuclear antibodies (ANA) and thyroid antibodies, such as antithyroid peroxidase (TPO) and antithyroglobulin, have also been reported in some fibromyalgia patients. These autoantibodies are commonly associated with autoimmune diseases like SLE and autoimmune thyroid disorders.

While the presence of autoantibodies in fibromyalgia patients is intriguing, it is important to note that the findings have been inconsistent across studies. Additionally, the mere presence of autoantibodies does not necessarily imply an autoimmune etiology, as they can also be found in healthy individuals or in conditions not related to autoimmunity.

Cytokine Levels

Cytokines are small proteins produced by various cells in the body, including those of the immune system. They play a crucial role in regulating inflammation, immune responses, and various physiological processes.

Several studies have investigated the levels of cytokines in fibromyalgia patients, with some reporting increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α). These cytokines have been implicated in the modulation of pain perception, fatigue, and depression, which are common symptoms in fibromyalgia.

However, other studies have found no significant dysregulation of cytokine production in fibromyalgia patients, indicating that alterations in cytokine levels may not be a dominant factor in the pathogenesis of the condition.

The conflicting findings regarding cytokine levels in fibromyalgia highlight the complexity of the immune system’s involvement and the need for further research to clarify the role of inflammation in the development and progression of the disorder.

Arguments for Autoimmune Etiology

Proponents of the autoimmune hypothesis in fibromyalgia cite several lines of evidence to support their viewpoint:

  1. Presence of Autoantibodies: The detection of various autoantibodies, such as anti-68/48 kD, anti-45 kD, ANA, and thyroid antibodies, in some fibromyalgia patients suggests a potential autoimmune component.
  2. Comorbidity with Autoimmune Diseases: The high prevalence of fibromyalgia in patients with autoimmune disorders like SLE, RA, and autoimmune thyroid diseases raises the possibility of shared pathogenic mechanisms or common underlying factors.
  3. Role of Neuroinflammation: Some researchers propose that fibromyalgia may involve a process of “neuroinflammation,” where inflammatory mediators and immune system activation lead to sensitization and dysregulation of nociceptive pathways, resulting in chronic pain and other symptoms.
  4. Neuroautoimmunity: Recent studies have explored the potential role of autoantibodies targeting specific neuronal or glial cells in the development of fibromyalgia symptoms, suggesting a neuroautoimmune component.

Arguments Against Autoimmune Etiology

On the other hand, opponents of the autoimmune hypothesis in fibromyalgia argue that the available evidence is insufficient to support this theory:

  1. Lack of Consistent Inflammatory Markers: Unlike in classic autoimmune diseases, there is no consistent evidence of systemic inflammation or tissue damage in fibromyalgia patients. Inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are typically within normal ranges.
  2. No Clear Autoimmune Pathophysiology: Despite extensive research, no clear autoimmune pathophysiological mechanism has been identified in fibromyalgia. The condition does not fit the classical pattern of autoimmune diseases, which typically involve specific organ or tissue damage mediated by autoantibodies or autoreactive immune cells.
  3. Lack of Response to Immunosuppressive Treatments: Fibromyalgia patients generally do not respond to immunosuppressive or anti-inflammatory treatments that are effective in managing autoimmune disorders, suggesting a different underlying mechanism.
  4. Biopsychosocial Model: Many experts support a biopsychosocial model for fibromyalgia, which proposes that the condition arises from the interplay of genetic, environmental, and psychosocial factors, rather than a primarily autoimmune etiology.

Which medical specialties should I seek?

When a patient suffers from chronic pain or believes they have symptoms of fibromyalgia, the best course of action is to seek a rheumatologist, who is a professional who treats diseases related to the musculoskeletal system and cares for bones, muscles, ligaments, and tendons.

It is important to seek this specialist, especially for a more correct interpretation of the tests. As mentioned before, the diagnosis of fibromyalgia is difficult to make and requires competent medical interpretation so that treatment can be started.

Why can the diagnosis of the disease take a long time?

The diagnosis of fibromyalgia can take a long time because of all the processes and tests that are necessary to confirm that it is really a case of this disease.

The symptoms of fibromyalgia are common to other types of diseases, and since they appear suddenly, their real cause needs to be investigated thoroughly, which ends up taking a long time.

One of the first steps is to investigate the pain locally through a physical examination. If the patient presents with psychological and neurological symptoms, it is also necessary to analyze the possible causes.

This psychological evaluation is necessary because it is believed that the pain caused by fibromyalgia is the result of an alteration in the brain’s perception of pain. Tests have shown a higher volume of pain neurotransmitters in people with fibromyalgia, which would explain the exaggerated reaction to pain.

Fibromyalgia can also appear associated with other rheumatic diseases, such as rheumatoid arthritis (an autoimmune disease in which the body attacks its own joints, causing pain and swelling). Because of this, tests such as CT scans and radiographs need to be studied carefully, as they may not be accurate indicators of the causes of a patient’s pain.

For these reasons, the process of diagnosing fibromyalgia can be time-consuming, which makes it difficult to start the appropriate treatment for a patient. In case of misinterpretation of the tests and symptoms, a patient may receive inadequate treatment, returning to feeling pain and having to live with this difficult condition.

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MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.

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