Faculty Affiliations and Disclosures 

Dr. Russell is associate professor of medicine and director of the University Clinical Research Center at the University of Texas Health Science Center in San Antonio, editor of the Journal of Musculoskeletal Pain, and emeritus founding president of the International MYOPAIN Society. Dr. Raphael is associate professor in the Departments of Psychiatry and Diagnostic Sciences at the University of Medicine and Dentistry of New Jersey in Newark.

Disclosures: Dr. Russell is a consultant to and on the advisory boards of Eli Lilly, Jazz, and Pfizer; is on the speaker’s bureaus of Ortho-McNeil and Pfizer; and receives research support from Eli Lilly, Jazz, Ortho-McNeil, and Pfizer. He is supported, in part, by the RGK Foundation of Austin Texas. Dr. Raphael is supported, in part, by National Institutes of Health grant DE13486. This article references unlabeled or unapproved uses of duloxetine, pregabalin, and sodium oxybate.

Submitted for publication: December 31, 2007. Accepted for publication: February 18, 2008.

Please direct all correspondence to: I. Jon Russell, MD, PhD, Department of Medicine, Mail Code 7868, University of Texas Health Center, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900; Tel: 201-567-4661; E-mail: russell@uthscsa.dcci.com.

Abstract

Fibromyalgia syndrome (FMS) presents with widespread soft tissue pain. Common comorbidities include severe insomnia, body stiffness, affective symptoms, irritable bowels, and urethral syndrome. A 1990 research classification depends on a history of widespread pain and prominent tenderness to palpation at 11 or more of 18 specific tender points. It is a criteria-based diagnosis rather than one by exclusion and can accompany other medical conditions. FMS occurs worldwide, and can present any age, but is most common in adult females. Although numerous studies and reviews contend that FMS may be caused by psychological stress such as sexual abuse, a critical epidemiological review fails to support that concept. Existing data suggest that some individuals with FMS may have a dysregulated physiological stress response system that predates the onset of symptoms.

Introduction

Fibromyalgia syndrome (FMS) is a common, chronically painful soft tissue pain condition. Affected individuals exhibit persistent, widespread pain and tenderness to palpation at anatomically defined tender points located in soft tissue musculoskeletal structures. Associated systemic symptoms can include insomnia, cognitive dysfunction, depression, anxiety, recurrent headaches, dizziness, fatigue, morning stiffness, extremity dysesthesia, irritable bowel syndrome, and irritable bladder syndrome.¹

Based on the 1990 American College of Rheumatology (ACR) classification criteria,² the diagnosis of FMS can be accomplished with confidence even in the presence of other medical conditions. There is still a need for a validated clinical case definition of FMS.³

The precipitating causes of FMS may vary among individuals, but the consensus is that central sensitization is responsible for an amplified perception of pain. As a result, this condition is recognized as the human model for chronic widespread allodynia. Biological abnormalities are detected in most patients, including dysfunctional sleep by polysomnography, temporal summation leading to second pain, lowered thresholds to pressure-induced pain demonstrable by brain imaging, low levels of the biogenic amines which fail to adequately drive descending inhibition, elevated spinal fluid levels of substance P, and, in primary FMS only, elevated spinal fluid levels of nerve growth factor.

While a cure is elusive, multimodal therapy is progressively more effective because it is focused on pathogenesis. It is predicted that the next 10 years will see validation of a clinical case definition, more interest in the underlying pathogenesis, a better understanding of how medical care should be adapted to subgroup variations, new medications with specific indications for FMS, strategic mechanism-directed polypharmacy, characterization of the genetic predisposition, and more emphasis on precipitating events.

The purpose of this review is to briefly describe the presentation, diagnosis, and differential diagnosis of FMS. In addition, it will review the arguments regarding a proposed relationship between victimization and FMS.

Classification of Soft Tissue Pain

FMS is just one of more than 100 named conditions that can cause body pain and interfere with mechanical function. It is logical to divide these nearly equally into two main categories: those that actively involve the joints (arthritis) and those that do not. There has been much confusion in terminology surrounding the latter group of disorders. Some of the confusion resulted from misunderstandings regarding the myofascial pain syndrome (MPS). Clinicians who had heard of MPS but were not skilled in its diagnosis generically used the term “myofascial pain” for a host of non-arthritic disorders. That term was problematic because it did not constitute a real diagnosis. The same is true for the term “nonarticular rheumatism.” The newer term is “soft tissue pain” (STP) disorders.⁴ Table 1 provides an abbreviated but useful classification of STP with the three main subheadings being “Local,” “Regional,” and “Generalized.”

Most of the “local” conditions are believed to have resulted from repetitive mechanical injury to inadequately conditioned tissues. They were named anatomically and are disclosed by a typical history plus the exquisite tenderness elicited by digital palpation of the affected structure. 

The “regional” syndromes are limited in anatomic scope to a region or body quadrant as seen with the MPS. This condition is again important to the discussion of terminology because it is characterized by trigger points (TrPs) in skeletal muscle.^5,6 A TrP that is manipulated by pressure or a needle hurts locally but also refers pain to another location, which is where the patient experienced the spontaneous pain.

The “generalized” category implies a systemic process like that of FMS, which affects the musculoskeletal system in a more global manner.  It is characterized by widespread pain and multiple strategically distributed tender points (TePs) that hurt locally but do not refer pain when manipulated.

Classification/Diagnosis of Fibromyalgia Syndrome

Before 1990, multiple criteria were used for the diagnosis of FMS, all of which likely identified the same type of individuals. The results of a multicenter research study sanctioned by the ACR2 led to the development of uniform research criteria for the classification of FMS. These criteria required only two simple components: a history of widespread pain for at least 3 months and somatic pain sensitivity to 4 kg of digital pressure at 11 or more of 18 anatomically defined TePs (Table 2). They exhibited moderately high sensitivity (88.4%) and specificity (81.1%) for FMS against normal controls and other painful disorders. These criteria have been criticized because they are largely subjective but their utilization has continued to grow.

Other Manifestations

Cognitive dysfunction is very disturbing to FMS patients and is most readily demonstrated with distraction or multitasking.⁷ Psychological distress is common among FMS patients, with depression or anxiety each found in 40%. Chronic, moderately severe insomnia is even more common, with 80% to 90% of FMS patients affected. Typically, the patients report being alert frequently during the night and awakening feeling unrefreshed. It is surprising that these chronically sleep-deprived individuals have difficulty napping during the day. The morning stiffness, which is perceived to be painful, lasts for 30 minutes to several hours every day. Approximately 80% of FMS patients complain of fatigue, which is qualitatively and quantitatively different from that of chronic fatigue syndrome. Other organ systems that can be involved include irritable bowel syndrome in ~40% and irritable bladder (urethral) syndrome or interstitial cystitis in ~12%. These manifestations clearly contribute to the suffering experienced by FMS patients.

Assessment of Pain Severity in Fibromyalgia Syndrome

Subjective Assessment

Self-assessment instruments typically use a form of the Visual Analog Scale to document subjective pain.⁸

Tender Points

The anatomic location of the somatic tenderness at the FMS TePs is deep to the skin in soft tissue structures, such as skeletal muscles, ligaments, and bursae, but there is still no convincing evidence that the painful tissues are histologically abnormal. According to the ACR criteria, at least 11 of the 18 TePs must exhibit painful sensitivity to 4 kg of digital palpation pressure. That amount of pressure can be standardized against a pressure gauge (algometer), but an approximation of the correct amount of pressure can be obtained by pressing the examining thumb against a surface until the blood flow to the mid to distal portion of the nail blanches. The reliability of this examination can be influenced by the amount of pressure applied and by the rate at which it is applied.^9,10 The amount of perceived discomfort can be accentuated and prolonged by applying the stimulus repetitively to induce windup. Patients with FMS will often react to pressure palpation of a TeP by withdrawal, diffuse activation of erector pili of the skin (cutis anserina), or by spontaneous lacrimation. The aching sensation may persist for days. There is no longer any role for the use of control points to exclude psychosomatic hysterical tenderness.

Epidemiology

FMS has been found in all ethnic groups studied to date. The syndrome is not limited to affluence or industrialized nations. With a prevalence ranging from 2% to ~12% in the general population, it must be viewed as a common medical condition.¹¹ Its prevalence increases with age, most dramatically in women with a peak in the fifth to seventh decade (7.4% to 10%). Adult women are affected four to five times more often than adult men. By contrast, the gender distribution of childhood FMS is nearly equal and many children outgrow their symptoms.¹² Approximately 15% of patients seen in rheumatology clinics are classified as having FMS, while the prevalence of FMS is ~6% in other practice settings. The annual direct cost of care for an individual FMS patient in the United States was >$2,200 in 1997.¹³ Multiplied by the 7 million FMS patients in the US, that figure predicts an annual direct cost of >$14 billion. 

Little is known about the incidence of FMS, but risk factors for its development may include physical trauma, a febrile illness, or a family history of FMS. A study conducted in Israel showed that automobile accidents with whiplash neck injury were more likely to antedate FMS than were industrial accidents with a bony fracture of a lower extremity (22% versus 2% for all subjects, >30% for female accident victims).¹⁴ A previously narrowed cervical canal may be an important risk factor for the development of chronic pain following a whiplash injury.¹⁵

Differential Diagnosis

Contemporary practice holds that when the 1990 ACR classification criteria are met, it is appropriate to classify the affected individual as having FMS irrespective of, or in addition to, any other legitimate medical diagnoses.

The main complaints of FMS patients pertain to body pain, so the differential diagnosis must consider a wide variety of other painful conditions (Table 3). Clues that suggest an overlap with severe psychological comorbidities, such as major depression, panic disorder, or other anxiety disorders must be carefully considered. At the first and every subsequent visit, it is incumbent upon the clinician to have his or her diagnostic senses alert to detect concomitant conditions that may present in an FMS patient.

FMS can accompany a variety of chronic medical conditions. In the past, FMS was believed to have resulted from the other condition, therefore it was called “secondary FMS.” When the 1990 ACR criteria were reported, it was noted that secondary FMS was not clinically distinguishable from “primary FMS.”² Increasingly, laboratory findings  do distinguish these FMS subgroups.¹⁶ Examples of people with secondary FMS include nearly 30% of patients with rheumatoid arthritis, 40% of systemic lupus patients, and 50% of Sjögren’s syndrome. Rheumatic disease patients whose high dosages of glucocorticoids are being rapidly tapered, and endocrine patients with Cushing’s syndrome whose glucocorticoid levels drop precipitously after successful surgery, can develop a form of FMS referred to as “steroid withdrawal FMS.” Gradual reduction of the levels may obviate this effect.

Conflicting Views Concerning Data on Fibromyalgia and Victimization

At first glance, data seem to support the concept that emotional trauma and sexual victimization are etiologically important in the development of FMS. Several studies using either self-report questionnaires¹⁷ or interviews^18,19 to assess abuse history suggested that patients with FMS had elevated rates of lifetime physical abuse and sexual abuse,¹⁷ overall victimization,¹⁸ or childhood adversities¹⁹ compared to patients with medically explained pain¹⁹ or other rheumatic disease.^17,18 Conversely, the authors of other questionnaire-based studies^20-22 concluded that rates of childhood abuse did not differ from comparison groups. The fact that there are negative findings in some studies indicates that such associations are not particularly large or robust. This conclusion is consistent with a weak relationship, if any, between childhood victimization and general pain in adulthood.²³

Finestone and colleagues²⁴ compared women attending a therapy group for victims of childhood sexual abuse versus a control sample consisting of psychiatric patients who did not report abuse histories to a control group composed of nurses. The former group was more likely than the control groups to report that they had received a diagnosis of FMS. Those reporting childhood sexual abuse also indicated greater medical resource utilization than did the controls. Methodological problems have been observed in the research on traumatic abuse and FMS. When one looks at the last two findings of Finestone and colleagues,²⁴ an important problem is illustrated: Receiving a diagnosis of FMS is highly selective and is likely dependent on the extent of health care that a symptomatic individual pursues. The diagnosis of FMS is much more likely to be made in the course of tertiary care than in primary care.²⁵ Thus, elevated rates of receiving a FMS diagnosis among those reporting a history of childhood abuse may have been secondary to the group’s increased healthcare utilization. Clinicians assessing their patients for a history of abuse, and even studies recruiting care-seeking patients, may suffer from the so-called “clinician’s illusion.”²⁶

Use of a community sample of individuals with FMS mitigates the sampling bias problem. A report by Ciccone and colleagues²⁷ examined lifetime sexual and physical abuse histories in a community sample of women who met ACR criteria for FMS. When compared with community women without FMS, self-reported sexual and physical abuse histories were not elevated among women with FMS. Similar findings were reported in other research.²⁸ Thus, prior studies reporting elevated rates of abuse in FMS patients have likely overestimated the relationship by focusing on care-seeking samples of individuals.

The second major weakness of most studies is their reliance on self-report of physical or sexual abuse. Reliance on retrospective reports of abuse has been criticized due to poor recall^29,30 and unreliability.³¹ Traumatic events of all types tend to be unreliably reported,³² especially when using typical questionnaire methods.³³  Recall bias can markedly inflate the apparent relationship between FMS and abuse.³⁴ This is illustrated by individuals with a complicated illness, such as FMS, exerting more effort than do controls to recall prior life events. Another example occurs when distressed individuals recall prior experiences in a mood-congruent way.³⁵

Fortunately, the problem of recall bias was not an issue for two prospective studies^36,37 that tested the relationship between court-documented abuse in childhood and pain in adulthood; neither study supported an association between the two. The discrepant conclusions arising when comparing court-documented abuse versus those resulting from self-reported abuse fail to inspire confidence in the relationship between childhood abuse and pain in adulthood.

A Model Based on Intrinsic Vulnerability to Stress

 Both self-report and court-documented abuse records do, however, confirm a relationship between childhood abuse and posttraumatic stress disorder (PTSD).³⁸ In a report that found that women with FMS symptoms were at increased risk for new PTSD following the September 11, 2001, terrorist attacks, we suggested the following³⁹ (despite the fact that onsets of FMS symptoms were unrelated to such traumatic exposures⁴⁰):

This view is consistent with the views of one of the leading researchers in PTSD, Rachel Yehuda, PhD, who points out that PTSD is best conceived as an extreme response to common stressful events rather than a common response to inherently traumatic events.⁴¹ Familial studies have suggested that FMS is associated with a variety of genetic polymorphisms in genes encoding for serotonergic and catecholaminergic systems relevant to physiological stress response systems.⁴² Some of the same gene regions identified in studies of FMS^43,44 have been identified in studies of depression, another syndrome that may involve stress vulnerability,⁴⁵ and suggest a genetic explanation for familial aggregation of depression in FMS.^46,47 Clearly, genetic risks predate even the earliest exposures to environmental stressors.

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