How to Handle Fibromyalgia



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Date Posted : 2011-01-20

How to Handle Fibromyalgia


Authors and Disclosures

Author(s) Jonathan Kay, MD

Professor of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; Director of Clinical Research, Division of Rheumatology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts

Disclosure: Jonathan Kay, MD, has disclosed the following relevant financial relationships:
Served as a advisor or consultant for: Array BioPharma Inc.; Bristol-Myers Squibb Company; Celgene Corporation; Centocor, Inc.; Roche; sanofi-aventis; UCB Pharma, Inc.
Received research grant from: Roche; sanofi-aventis

Charles E. Argoff, MD

http://www.medscape.com/viewarticle/735369?src=mp&spon=27

Professor, Department of Neurology, Albany Medical College, Albany, New York; Director, Comprehensive Pain Program, Albany Medical Center, Albany, New York

Disclosure: Charles E. Argoff, MD, has disclosed the following relevant financial relationships:
Owns stock, stock options or bonds from: Pfizer Inc.
Received grants for clinical research from: Eli Lilly and Company; Endo Pharmaceuticals; Forest Laboratories, Inc.
Served as an advisor or consultant for: Covidien; Eli Lilly and Company; Endo Pharmaceuticals; Forest Laboratories, Inc.; King Pharmaceuticals Inc.; Pfizer Inc.; PriCara; sanofi-aventis; Solvay Pharmaceuticals, Inc.

From Medscape Rheumatology

Is Fibromyalgia Real?

Jonathan Kay, MD; Charles E. Argoff, MD

Posted: 01/10/2011

Editor's Note: What exactly is fibromyalgia? And what causes it? Medscape invited Dr. Charles Argoff, a neurologist specializing in pain, and Dr. Jonathan Kay, a rheumatologist, to debate via email this controversial and complex issue.

What Is Fibromyalgia?

Jonathan Kay, MD: "Fibromyalgia" is a label that has been given to a large number of patients who experience chronic pain. A small subset of these patients have characteristic tender points, but the vast majority of patients who carry this label describe diffuse pain that is not more pronounced when specific areas are palpated. The vast majority of these patients also describe migraine headaches, shooting pains in their extremities, chronic fatigue, and sleep disturbances. Some report alternating constipation and diarrhea, which usually is labeled as being "irritable bowel," but others do not experience these gastrointestinal symptoms.

Also, patients with inflammatory arthritis or early fibrosing syndromes may experience pain in multiple areas without manifesting detectable signs of joint inflammation or tissue fibrosis. Some of these patients may be labeled as "fibromyalgia," but display signs of more typical disease as time passes. Other conditions, such as certain endocrinopathies, may also present with fatigue, generalized aching, and other symptoms that prompt giving these patients the label of "fibromyalgia."

Although a few patients may present with increased tenderness over characteristic tender points, fatigue, migraine headaches, shooting pains in the extremities, fatigue, and irritable bowel syndrome symptoms, without another obvious diagnosis, it is clear that "fibromyalgia" is not by itself a distinct condition with a single pathophysiologic mechanism. Rather, it is a common symptom complex that is characteristic of the heightened perception of pain associated with a number of different precipitating factors.

Charles Argoff, MD: Clinicians should be accustomed to being faced with managing conditions for which absolute knowledge regarding the conditions and their etiology and pathophysiology are not known. In fact, this is true for most medical conditions we encounter including many nonpain-related conditions such as hypertension, various cancers and diabetes. Even the wisest among us cannot state with absolute certainty the exact cause(s) of fibromyalgia syndrome and/or its mechanisms(s). Fibromyalgia syndrome is not a label to be applied to another human being. It is a common chronic medical condition associated with widespread pain, lowered pain thresholds, and augmented sensory perception. Recent efforts by the American College of Rheumatology have focused attention as well on the nonpainful aspects of fibromyalgia syndrome such as fatigue and sleep disturbances as important diagnostic features.

Dr. Kay: I agree with Dr. Argoff that clinicians often face and manage conditions for which the etiology is unknown. In rheumatology, we do not know the etiology of most rheumatic diseases. However, the pathophysiology of most diseases that we treat is understood, at least to the extent that there is some understanding of the mechanism by which therapies interfere with the disease process.

I disagree with Dr. Argoff that the pathophysiology of "fibromyalgia" syndrome is not known. No specific pathophysiology is ascribed to the label of "fibromyalgia"; however, patients develop the symptoms of this syndrome in association with various underlying disorders. Applying the label of "fibromyalgia" syndrome to the syndrome of widespread pain, lowered pain thresholds, and augmented sensory perception without attempting to identify an underlying pathophysiologic process makes treatment of patients with this symptom complex more difficult than necessary. Considering sleep disturbances, for example, to be "aspects" of the syndrome rather than predisposing factors is "chicken and egg" logic. It is important to acknowledge which comes first, so that the predisposing factor may be treated to prevent the resulting symptoms.

Dr. Argoff: Given that all patients currently diagnosed with fibromyalgia do not have completely identical symptoms including the fact that not all patients share the same sleep disturbances, Dr. Kay's comments actually underscore the complexity of managing the person with fibromyalgia as well as the urgent need to learn more about its pathophysiology, which is currently incompletely understood.

What Causes Fibromyalgia?

Dr. Kay: The fibromyalgia symptom complex can result from a number of different etiologies. The vast majority of patients labeled as having "fibromyalgia" describe a disturbed sleep pattern, either as a primary process or resulting from their underlying pain syndrome. Many obese patients who experience a heightened perception of pain have obstructive sleep apnea that either has not been diagnosed or is inadequately treated. A number of patients, many of whom have normal body mass indices, describe symptoms of restless legs syndrome. Those patients may have associated iron deficiency and often report family members who also have restless leg syndrome.

Dr. Argoff: Fibromyalgia is a medical condition whose diagnosis can be made based upon established diagnostic criteria. It may coexist and, in fact, often interrelates with other medical conditions including rheumatoid arthritis and others. Mental health comorbidities are common but are not the cause of fibromyalgia.

Dr. Kay: Certainly, patients with symptoms that are labeled as "fibromyalgia" syndrome may have other medical conditions, including rheumatoid arthritis and other forms of inflammatory joint disease. I also agree with Dr. Argoff that mental health comorbidities are common among patients with "fibromyalgia" syndrome. However, having stated that the "etiology and pathophysiology" of "fibromyalgia syndrome are not known," how can he then assert that mental health comorbidities are not the cause of "fibromyalgia," if "even the wisest among us cannot state with absolute certainty the exact cause(s) of fibromyalgia syndrome?" My esteemed colleague seems to be engaging here in a circular argument.

Dr. Argoff: Given that all patients currently diagnosed with fibromyalgia do not meet current diagnostic criteria for major depressive disorder or any other mental health disorder per se, and given that it is well documented that treatment benefit from serotonin-norepinephrine reuptake inhibitor (SNRI) agents is independent of whether or not an individual is depressed or not, it is clear that mental health comorbidities are not the cause of fibromylagia since they don't occur in all patients.

Is Abuse To Blame?

Dr. Kay: A disturbingly high number of patients with chronic pain that has been labeled as "fibromyalgia," upon direct questioning, report having been victims of preadolescent sexual abuse, often at the hands of close relatives or of others who abuse their position of authority and responsibility. Others report having been in an abusive relationship.

Unfortunately, many patients who are victims of spousal abuse are accompanied to their medical visit by the abusive spouse who is trying to prevent them from disclosing the nature of this relationship. Thus, a large number of patients who are labeled as having "fibromyalgia" actually have a posttraumatic syndrome that manifests with a heightened perception of pain and associated symptoms. Interestingly, these patients typically report migraine headaches, shooting pains in their extremities, and fatigue, but no alternating constipation and diarrhea.

Dr. Argoff: Victims of preadolescent sexual abuse are noted to experience autoimmune diseases, chronic migraine and other headache syndromes, and hypertension, to name just a few medical conditions. In other words, those individuals who are unfortunate victims of such horrifically traumatic experiences are at risk of developing many medical consequences, including but not restricted to fibromyalgia syndrome.[1-3] Being aware of a person's history of preadolescent sexual abuse does not diminish the legitimacy of the medical condition that has emerged in any way whatsoever.

Dr. Kay: I am unaware of any evidence that demonstrates an autoimmune disease to result from preadolescent sexual abuse. Certainly, victims of such abuse develop chronic migraine headaches and other features of "fibromyalgia" syndrome as part of a posttraumatic syndrome. It is important for medical professionals to be aware of physical and sexual abuse to which patients have been subjected and to make certain that individuals are removed from the setting in which they are subject to such abuse. In no way does a history of physical or sexual abuse diminish the legitimacy of any objective medical condition.

Dr. Argoff: There are numerous peer-reviewed articles that have examined this relationship.[1-3]

Dr. Kay: The papers cited by Dr. Argoff support my assertion that many patients who are labeled as having "fibromyalgia" actually have a posttraumatic syndrome that manifests with a heightened perception of pain and associated symptoms. This is exactly the point made by Dr. Walker and his colleagues and Dr. Wilson. [2,3] In the abstract of her review article, Dr. Wilson defines "autoimmune disorders" as irritable bowel syndrome, asthma, and fibromyalgia. Most rheumatologists would disagree with her classifying these 3 conditions as "autoimmune" and would instead classify them as belonging to the spectrum of "central sensitivity syndromes."[4] The study by Drs. Goodwin and Stein used a self-report checklist form to query participants in the National Comorbidity Survey as to the presence of "physical illnesses" within the past 12 months. One of the categories asked about "thyroid disease, or other autoimmune disorders." Although the adjusted odds ratio for an association between self-reported physical abuse and self-reported "autoimmune disease" ranged from 1.7 to 3.1, this self-diagnosis of "autoimmune disease" is of questionable legitimacy given that the patients' self-diagnoses were not validated and the absence of a definition for "autoimmune disease" on the checklist.[1] Thus, there remains no convincing evidence to demonstrate that an autoimmune disease results from preadolescent sexual abuse.

So Is It Depression?

Dr. Kay: A very small number of patients who carry the label of "fibromyalgia" actually have inadequately treated depression. With appropriate adjustment of their psychopharmacologic regimen, the somatic symptoms that are labeled as "fibromyalgia" come under better control.

Dr. Argoff: Mental health comorbidities are common but are not the cause of fibromyalgia. It is well established in the medical literature that many antidepressants have analgesic properties that have been conclusively demonstrated to be independent of their antidepressant properties. Two such agents are currently US Food and Drug Administration (FDA)-approved for the treatment of fibromyalgia syndrome.

Dr. Kay: I do not assert that depression or other mental health conditions are the cause of "fibromyalgia" syndrome. Dr. Argoff is correct in his statement that antidepressant medications have analgesic properties that are independent of their antidepressant properties. The FDA has approved both pregabalin and milnacipran for the treatment of patients with "fibromyalgia" syndrome. Although milnacipran is also approved for the treatment of major depressive disorder, pregabalin is not an antidepressant medication.

Dr. Argoff: There are 3 FDA-approved medications for the treatment of fibromyalgia. Two of them, duloxetine and milnacipran, are considered SNRI agents but only 1 of these, duloxetine, is also approved by the FDA for major depressive disorder and/or generalized anxiety disorder. Minalcipran is not approved by the FDA for any mental health indication. The European Medicines Agency (EMEA) however has approved milnacipran for the treatment of major depression, and it has been used in Europe for many years for this purpose. Pregabalin is an example of an alpha(2)-delta agonist medication, and it is not an antidepressant nor did any of my prior comments suggest otherwise!

Where Does This Leave Us?

Dr. Kay: Dr. Argoff and I agree that "fibromyalgia" syndrome is a condition in which patients experience chronic diffuse pain, typically accompanied by migraine headaches, shooting pains in their extremities, and chronic fatigue. It is frustrating to both the patient and the physician that this constellation of symptoms does not have a single cause and that its pathophysiology remains incompletely understood. Many patients with this condition do not have mental health comorbidities, yet they may respond to treatment with SNRIs.

We disagree about the relationship between preadolescent sexual abuse and the subsequent development of autoimmune disease. Although Dr. Argoff states that "numerous peer-reviewed articles... have examined this relationship," the "autoimmune disorders" included were "irritable bowel syndrome, asthma, and fibromyalgia."[3] None of these conditions is associated with autoantibody production and none is typically considered to be an autoimmune disease.

Regardless of how one categorizes its pathophysiology, individuals with chronic diffuse pain suffer with their symptom complex. As physicians, we must try our best to relieve their distress. Understanding the specific pathophysiologic basis for a patient's chronic pain helps to direct treatment: therapies that address underlying causes of heightened pain perception are more likely to be successful than those which merely lessen symptoms. However, the questions raised by our dialogue highlight some of the unanswered questions about "fibromyalgia" syndrome that warrant clarification by well-designed research studies.

Dr. Argoff: It has been an honor to participate in this virtual debate and I agree with Dr. Kay that only with continued quality research efforts can we hope to clarify so many of the details of fibromyalgia and its care.

References

  1. Goodwin RD, Stein MB. Association between childhood trauma and physical disorders among adults in the United States. Psychol Med. 2004;34:509-520.
  2. Walker EA, Keegan D, Gardner G, Sullivan M, Bernstein D, Katon WJ. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: II. Sexual, physical, and emotional abuse and neglect. Psychosom Med. 1997;59:572-577.
  3. Wilson DR. Health consequences of childhood sexual abuse. Perspect Psychiatr Care. 2010;46:56-64.
  4. Yunus MB. Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum. 2007;36:339-356.

Medscape Rheumatology © 2011 WebMD, LLC



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