AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Fibromyalgia is a complex disorder defined only recently, but it is not recently discovered. Descriptions have been found in the medical literature as far back as the early 17th century. Many physicians prefer not to deal with patients who have this complicated disorder and question its existence. In the past, poor recognition and lack of treatment for fibromyalgia could be explained by a lack of meaningful research. Today, abundant research and medical evidence supports the diagnosis of fibromyalgia.

Some experts propose that physicians make a paradigm shift in their approach to successfully caring for patients with fibromyalgia. We can no longer rely on the technological advances of science. Even with advanced imaging and laboratory tests, none of the findings confirms the diagnosis of fibromyalgia. A physician skilled in taking a careful history, listening to the patient's concerns, and performing a thorough examination remains the foundation for diagnosing and treating fibromyalgia. The physician must remain a scientist and practice evidence-based medicine without abandoning the Hippocratic principles in the Physician's Oath. We must keep our promises of caring for and serving the sick and the suffering without prejudicial views.

Definition of fibromyalgia

Fibromyalgia, a common disorder, is a syndrome composed of a specific set of signs and symptoms. Fibromyalgia has long been considered a "wastebasket" diagnosis. However, in 1987, the American Medical Association (AMA) acknowledged fibromyalgia as a true illness and a potential cause of disability. Many well-respected organizations, such as the AMA, the National Institutes of Health (NIH), and the World Health Organization (WHO) have accepted fibromyalgia as a legitimate clinical entity (Starlanyl, 1996). Fibromyalgia is now recognized as one of many central pain-related syndromes that are common in the general population. Recent advances have lead to the conclusion that disturbances within the central nervous system (CNS) known as central sensitization represent the most likely source.

Patients with fibromyalgia generally see many physicians before receiving a correct diagnosis. Patients may seek medical advice for more than 5 years before a correct diagnosis is made, and more than 50% of patients receive a misdiagnosis and may undergo unnecessary surgery.

Nomenclature

Although the syndrome has been known by other names, the word fibromyalgia was first introduced in 1976. This word is derived from the Latin roots fibro (fibrous tissue), my (muscles), al (pain), and gia (condition of). Fibromyalgia was most commonly known by the misnomer fibrositis, where -itis implied an inflammatory component. Chaitrow asserts that no inflammatory process has ever been found to be a part of this disease.

Pathophysiology

Although the sequence of events that causes fibromyalgia remains unknown, advances and discoveries may help to unravel the mysteries of this disease. Research shows biochemical, metabolic, and immunoregulatory abnormalities associated with fibromyalgia.

Although the pathogenesis of fibromyalgia is not completely understood, the currently known abnormalities substantiate the proposal that fibromyalgia can no longer be considered a subjective pain condition. The biochemical changes seen in the CNS, the low levels of serotonin, the 4-fold increase in nerve growth factor, and the elevated levels of substance P all lead to a whole-body hypersensitivity to pain and suggest that fibromyalgia may be a condition of abnormal central processing of nociceptive pain input or central sensitization. Ongoing research will continue to provide a clearer picture of the pathophysiology of this complex syndrome.

Central processes

Clinicians can enhance their approach to diagnosis and treatment by broadening their knowledge of these biochemical and immunoregulatory abnormalities, which may be involved in how nociceptive signals to the CNS are interpreted and how they individuals physiologically respond to stress.

Our current understanding of the pathophysiology of fibromyalgia is that the disease is a disorder of central pain processing or a syndrome of central sensitivity. Daniel Clauw, a rheumatologist and fibromyalgia researcher, describes the syndrome as a diffuse problem of sensory volume control that alters the patient's threshold to pain and to other stimuli, such as heat, noise, and strong odors. He also suggests that patients may have hypersensitivity because of neurobiologic changes that affect the perception of nociceptive pain or because of expectancy or hypervigilance, which may be related to psychological factors.

Plasticity in the function of N-methyl-D-aspartate (NMDA) subtype glutamate receptors is necessary for central sensitization to occur. Increased sensitivity of central NMDA receptors were implicated by earlier studies as playing a primary role in fibromyalgia. However, more recent evidence suggests that suppression of the normal activity of dopamine-releasing neurons in the limbic system is the primary pathology in fibromyalgia. Increasing evidence indicates that fibromyalgia may represent a dysregulation of dopaminergic neurotransmission.

Serotonin

The most widely acknowledged biochemical abnormality associated with fibromyalgia is abnormally low serotonin levels. Many studies have linked serotonin, a neurotransmitter, to sleep, pain perception, headaches, and mood disorders. Lower-than-normal levels of serotonin have been observed in patients with fibromyalgia. A low platelet serotonin value is believed to be the cause of the low serum levels, which have been correlated with painful symptoms.

Serotonin levels in the CNS are thought to be low because of low levels of tryptophan (amino acid precursor to serotonin) and 5-hydroxyindole acetic acid (metabolic by-product) in the spinal fluid. Investigators have proposed a link between low serotonin levels and symptoms of fibromyalgia. Moreover, many propose that low serotonin levels may cause fibromyalgia in whole or in part.

Substance P

In support of the idea of a systemic biochemical abnormality in fibromyalgia, investigators from 4 independent studies reported levels of substance P that were elevated by 2-3 times.

Substance P, the neuropeptide in spinal fluid, is a neurotransmitter that is released when axons are stimulated. Increased levels of substance P increase the sensitivity of nerves to pain or heighten awareness of pain. The elevated levels in the spinal cord cause fairly normal stimuli to result in exaggerated nociception. Some authors believe that neither elevated substance P levels nor low serotonin levels alone can be primary cause. Instead, the dual dysfunction may be responsible for fibromyalgia.

Adenosine triphosphate

Researchers also have found low levels of adenosine triphosphate (ATP) in red blood cells of patients with fibromyalgia. Although the significance is unknown, some suggest that low platelet serotonin levels can be explained if platelet ATP levels are also low. ATP is necessary to move and then hold serotonin in platelets. More investigation into ATP and the link to serotonin is needed.

Dysfunction of the hypothalamic-pituitary-adrenal axis

Some have studied the neuroendocrine aspects of fibromyalgia and found dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is a critical component of the stress-adaptation response. In a normally functioning system, corticotropin-releasing hormone (CRH) stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal cortex to produce glucocorticoids, which are powerful mediators of the stress-adaptation response.

Circadian regulation and the stress-induced stimulation of the HPA axis are, in part, regulated by serotonin. Perturbations in serotonin metabolism (as well as premorbid abnormalities of the HPA axis) may explain the abnormalities of the HPA axis in fibromyalgia.

Dysfunction of the HPA axis may exaggerate the effects of abnormal serotonin metabolism. Hypoactivity of the HPA axis may cause low central serotonin levels.

Some authors have noted that 5 main measurable neuroendocrine abnormalities are associated with dysfunction of the HPA axis: (1) low free cortisol levels in 24-hour urine samples, (2) loss of the normal circadian rhythm with elevated evening cortisol level (when it should be at its lowest level), (3) insulin-induced hypoglycemia associated with an overproduction of pituitary ACTH, (4) low levels of growth hormone, and (5) stimulated ACTH secretion leading to insufficient adrenal release of glucocorticoids.

Growth hormone

Growth hormone, produced during delta sleep, is involved in tissue repair. Therefore, disrupted stage 4 (delta) sleep associated with fibromyalgia may account for low levels of growth hormone. Growth hormone stimulates the production of insulinlike growth factor I (IGF-I) in the liver. Some authors have found that most patients with fibromyalgia have low levels of IGF-I and that low levels are both specific and sensitive for fibromyalgia.

Nerve growth factor

In some studies, nerve growth factor was 4 times higher in the spinal fluid of patients with fibromyalgia than in others. This factor is important to the pathophysiology of fibromyalgia because the process enhances the production of substance P in afferent neurons, increasing the person's sensitivity or awareness to pain. Nerve growth factor also may play a role in spreading or redistributing perceived pain signals.

Genetic predisposition

Increasing evidence suggests that both genetic and environmental factors play a role in the etiopathology of fibromyalgia. The most probable mode of inheritance is polygenic. According to Jane Olson, early results of studies involving more than 140 families may confirm that the genes associated with serotonin play a role in fibromyalgia (Olson, 2004). According to some evidence, the etiology of fibromyalgia may involve polymorphisms of genes in the serotonergic, catecholaminergic, and dopaminergic systems. Future genetic studies are needed in the fields of fibromyalgia and related conditions.

Some investigators suggest that the genetic predisposition manifests when the person reaches a critical age or when he or she sustains an external insult, such as trauma or illness.

Frequency

United States

At any given time, conservative estimates suggest that 2% of the general population meet the criteria for the diagnosis of fibromyalgia; this percentage includes including children, 3.4% of women and 0.5% of men.

As a result, fibromyalgia the second most common disorder that rheumatologists encounter. Physicians may find that approximately 8% of their patients have fibromyalgia. In a rheumatology and physiatry practice, however, as many as 15% of evaluated patients have fibromyalgia. This incidence implies that 1 of every 10 patients evaluated in a medical practice has fibromyalgia.

International

Researchers from around the world have reported fibromyalgia.

Mortality/Morbidity

Some have compared the social, emotional, economic, and functional effect of fibromyalgia on an individual's life with the effects of rheumatoid arthritis.

• Approximately one third of patients with fibromyalgia reportedly modify their work to keep their jobs. Some patients shorten their workdays, their workweeks, or both. Many patients with fibromyalgia changed to jobs that are less physically and mentally taxing than their previous ones. This change often leads to decreased income and increased financial burdens.
• One report suggests that approximately 15% of the people with fibromyalgia are receiving disability benefits. Disability rates as high as 44% are reported.
• An estimate of the overall annual cost of this disease to the American economy is over $9 billion.

Race

No racial predilection exists in fibromyalgia. Researchers have reported the condition in all ethnic groups and cultures.

Sex

Fibromyalgia is 4-7 times more common in women than in men. No universally accepted explanation exists for this predilection, as differences between boys and girls are hardly recognized.

Age

Fibromyalgia may be diagnosed in individuals of all ages. Symptoms usually arise in those aged 20-55 years, but the condition may be diagnosed in childhood.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

Although insurance reimbursement and the other infrastructures are often barriers to giving patients the necessary time, a thorough and detailed history saves time in the long run, reduces the potential for litigation, helps prevent incorrect diagnosis, and eliminates inappropriate or unnecessary treatments. Without a thorough history, it is impossible to develop a complete list of the comorbid illnesses and inevitably results in incomplete and often inappropriate treatment. Patients with fibromyalgia do significantly better when they receive a comprehensive, individualized treatment regimen than when they do not, and a thorough history is the first step in developing that regimen.

Start the evaluation with identifying the chief complaint, which usually is pain. However, avoid treating patients based on the chief complaint alone. Premature treatment may lead to symptom chasing and ineffective treatment. Patients with fibromyalgia experience changes in symptoms from day to day, a feature that may not reflect the global nature of their disorder. This waxing-and-waning or fluctuating pattern of the symptoms is common in fibromyalgia.

Next, expand on the chief complaint by asking specific questions about the patient's pain. Question the patient about the distribution of pain (eg, ask whether the pain is regional or generalized). Ask about the duration and onset of the pain. Patients can usually remember a sudden onset of pain. If the pain began gradually, determining the exact time of onset is difficult. Inquire about aggravating and alleviating factors. Record the description or characteristics of the pain (eg, ask whether the pain is migratory, burning, tender, sore, aching, sharp, or radiating).

Question the patient about his or her sleep habits and environment. If possible, ask the patient's sleeping partner if the patient snores or kicks while asleep. Inquire about how long it takes for the patient to fall asleep and how many times he or she awakens. Ask patients how they feel in the morning.

Pellegrino and the present author suggest that physicians obtain information about the patient's diet, particularly their caffeine and carbohydrate intake.

The history should include any symptoms that may indicate the presence of 1 or more coexisting conditions (see Associated conditions below). Information on medications, exercise, and fatigue is also important. List any allergies and perpetuating factors. See also Clinical presentation below.

The patient's history of pain can be summarized as follows:

• Widespread pain
• • Right and left sides of the body
  • Above and below the waist
  • Along the axial skeleton
• Duration of pain
• • Constant
  • More than 3 months

Diagnostic criteria

Before 1990, no guidelines for evaluating and diagnosing fibromyalgia existed. Until recently, no medical or imaging tests were available to definitely diagnose fibromyalgia. A new blood test involving antipolymer antibodies has been developed. Approximately 50% of patients with fibromyalgia have these antibodies. This blood test provides objective evidence to identify a subgroup of people with fibromyalgia. Routine laboratory tests and radiography can help evaluate suspected coexisting conditions or rule out other possible diseases.

To reduce misdiagnosis and confusion, the American College of Rheumatology (ACR) recognized the need to establish a clear definition and guidelines. They sponsored a multicenter study to develop these criteria. In 1992, at the Second World Congress on Myofascial Pain and Fibromyalgia, the diagnostic criteria were expanded and refined.

The diagnostic criteria include 2 basic requirements. The first is the presence of pain in all 4 quadrants of the body, as well as in the axial skeleton on a more-or-less continuous basis for at least 3 months. The pain often is described as widespread or global.

The second criterion is the presence of at least 11 of 18 anatomically specific tender points (see Physical below). A tender point hurts only at the area where pressure (enough to cause the examiner's nail bed to blanch, or about 4 kg) is applied, and there is no referred pain. An instrument known as a dolorimeter can be used to apply exactly 4 kg of pressure over the tender points during the examination. The 18 possible tender points exist as 9 pairs. Tender points may be found in any palpable muscle, but 18 sites are consistently present in patients with fibromyalgia and are used for diagnosis. The ACR criteria describe 4 pairs of tender points on the anterior of the body and 5 pairs on the posterior of the body.

Clinical presentation

The typical patient has seen an average of 15 physicians and has had the fibromyalgia for approximately 5 years before receiving a correct diagnosis. Many cases are misdiagnosed, and many patients endure costly treatments that provide little benefit. At some point, most patients have been told that nothing is medically wrong and that the condition is imagined. Therefore, many patients become frustrated and skeptical. Although most are relieved when a correct diagnosis is finally made, the clinician may need to convince the patient that he or she actually knows what is wrong and treatment plan has been formulated.

Most patients with fibromyalgia are female and do not appear chronically ill. They may look fatigued or agitated. Their chief complaint is often "I hurt all over all the time." The quality of their constant pain is described as burning, aching, and soreness. They may feel as if they are bruised all over but without visible signs. Although the pain is constant, the location migrates and the intensity varies. Many patients may complain of only a single painful area, such as the low back or neck.

A careful history reveals that their pain is not focal in its distribution but global. Patients may initially complain of pain at 1 site because they are primarily concerned about their worst pain. Because many patients do not understand that the symptoms are connected, they give a fragmented history. The physician must ask the right questions to develop a complete understanding of the patient's distribution of pain.

Patients generally do not tell the physician that they have a sleeping disorder. Again, a carefully taken history reveals unrefreshing sleep in about 65% of patients and morning fatigue in about 80%. Patients awaken as tired as they were before sleeping. Most patients awaken frequently throughout the night, and some have difficulty falling asleep. They finally fall asleep in the early morning hours, describing this as their best sleep. Many patients fall asleep immediately, deny sleep onset problems, and report only infrequent awakenings. Sleep onset this rapid is abnormal and should not be overlooked.

Most patients complain of morning stiffness of variable duration. Question the sleeping partner about leg movements. Approximately 20% of patients have concomitant restless-legs syndrome, which may lead the physician to choose or add medications other than antidepressants.

The patients report their fatigue is second only to pain. The fatigue is worse in the morning and early evening. By ten or eleven o'clock in the morning, the fatigue subsides somewhat. Several investigators, including the present author, have found that poor sleep, physical activity, and diet can worsen the patient's fatigue.

Patients may not admit to feeling depressed or anxious; therefore, the physician must inquire about these conditions. The source of their emotional stress may be multifactorial.

Approximately 50% of patients present with complaints of tissues feeling swollen and numbness and tingling in the extremities. These symptoms generally are more common in the upper extremities than in the lower extremities. Objective swelling, sensory changes, and other neurologic findings are usually absent.

Some investigators list many other common complaints, including chronic headaches and tenderness of the scalp to the touch. Complaints of chest pain, shortness of breath, and palpitations are common. Serious cardiac problems should be considered and may require extensive evaluation. Many of these patients' symptoms are related to mitral valve prolapse syndrome.

Approximately 40% of patients with fibromyalgia describe symptoms of alternating diarrhea and constipation, bloating, cramping, and an increased urge to defecate. These symptoms are most likely related to irritable bowel syndrome. Some patients also may complain of symptoms that include urgency, frequency, and a sense of incomplete voiding. Pelvic pain and dysmenorrhea may be present as well.

Associated conditions

Several medical conditions and diseases frequently occur with fibromyalgia. In 1984, Dr Yunus used a Venn diagram to depict the interrelationships of these syndromes. He proposed that the syndromes are interconnected, similar, and overlapping, with a probable common pathophysiologic mechanism. Ironically, they have been described as functional syndromes. This is a misnomer because their pathophysiology is based on dysfunction of the neuroendocrine system. Central sensitization is likely the common pathophysiologic pathway.

These coexisting conditions can aggravate and perpetuate the patient's symptoms. If unrecognized, the physician might inadvertently prescribe an ineffective or even harmful treatment regimen, leading to costly and unnecessary testing.

The conditions most commonly associated with fibromyalgia include the following:

• Irritable bowel syndrome
• Tension/migraine headaches
• Dysmenorrhea
• Nondermatomal paresthesia
• Temporomandibular joint syndrome
• Mitral valve prolapse
• Interstitial cystitis, vulvodynia
• Female urethral syndrome
• Vulvar vestibulitis
• Hypermobility syndrome
• Restless-legs syndrome
• Allergy
• Multiple chemical sensitivity syndrome
• Enthesopathies
• Vestibular disorders
• Esophageal dysmotility
• Ocular disturbances
• Anxiety disorders
• Pulmonary symptoms
• Raynaud phenomenon
• Thyroid dysfunction
• Lyme disease
• Silicone breast implant syndrome
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Sjögren syndrome
• Infections
• Osteoarthritis
• Chronic fatigue syndrome
• Carpal tunnel syndrome
• Hyperventilation
• Premenstrual syndrome (PMS)
• Sleep disorders (see Sleep disorders below)
• Depression (see Depression below)
• Myofascial pain syndrome (see Myofascial pain syndrome below)
• Cognitive dysfunction (see Cognitive dysfunction below)
• Sleep disorders
• • Sleep is not a state of massive system shutdown but the contrary. During sleep, the brain is active, constantly communicating with the body. Many neurohormones, antibodies, and other molecules are synthesized during sleep; therefore, when sleep is disrupted, biochemical abnormalities can occur, leading to multisystem disturbances.
  • Sleep studies have shown that patients with fibromyalgia have disordered sleep physiology. Most of these patients experience unrefreshing sleep with morning fatigue.
  • To understand abnormal sleep architecture, it is essential to know the basics of normal sleep. Sleep can be divided into 2 main parts: non–rapid eye movement (NREM) and rapid eye movement (REM), which alternate cyclically through the night, always starting with NREM sleep. In each successive cycle through the night, NREM sleep decreases, and REM sleep increases. Each cycle, NREM plus REM, lasts about 90 minutes.
  • NREM is divided into 4 stages: stage 1 is initial drowsiness; stage 2, light sleep; and stages 3 and 4, progressively deeper levels of sleep. In stages 3 and 4, the EEG shows delta waves, which are high-amplitude (>75 mV) waves that move slowly (0.5-2 Hz). Much of the body's regulatory work, as well as synthesis of many substances (eg, antibodies, growth hormone, other neurochemicals), occurs during NREM sleep.
  • REM sleep has a low-voltage mixed-frequency pattern on EEG and is considered dream sleep. In this stage, the body has a complete loss of muscle tone, known as flaccid paralysis, and it cannot move. During this part of sleep, consolidation of memories may occur, but disagreement still exists regarding what occurs with memory during REM sleep. Some investigators found that, during waking hours, the brain generates alpha waves with a frequency of 7.5-11 Hz.
  • Sleep dysfunction is considered an integral feature of fibromyalgia. About 70% of patients recognize a connection with poor sleep and an increased pain, along with feeling unrefreshed, fatigued, and emotionally distressed. Several studies have linked abnormal sleep with these symptoms.
  • Researchers have studied fibromyalgia and sleep, confirming the disordered sleep physiology in fibromyalgia. This abnormality has been identified as a sleep anomaly of alpha-wave intrusion, which occurs during NREM stage 4 sleep. This intrusion into deep sleep causes the patient to awaken or to be aroused to a lighter level of sleep.
  • Some describe the altered sleep physiology and somatic symptoms as a nonrestorative sleep syndrome. This dysfunction is believed to be linked to the numerous metabolic disturbances associated with fibromyalgia, including abnormal levels of neurotransmitters (serotonin, substance P) and neuroendocrine and immune substances (growth hormone, cortisol, interleukin-1). These metabolic imbalances are thought to be responsible for the increased symptoms associated with this sleep disorder of alpha-wave intrusion by impairing tissue repair and disturbing the immunoregulatory role of sleep.
  • Most alpha-wave intrusions occur during the first few hours of sleep, decreasing throughout the night to normal levels by early morning. This hypothesis has been well correlated with patients' frequent reporting that their best sleep is obtained in the early-morning hours just before arising.
• Depression
• • Depression in fibromyalgia is a controversial topic. In support of the contention that fibromyalgia is not a psychiatric illness, some authors believe that symptoms of fibromyalgia are not corrected with psychological factors. Others have determined that fibromyalgia is not a psychiatric disorder. The depression associated with fibromyalgia is believed to result from the pain, sleep deprivation, and dysfunction.
  • Depression in fibromyalgia may be treated with a regimen that includes nonpharmaceutical therapies. Treating depression alone does not cure fibromyalgia. Antidepressants may help, but the clinician also should address other symptoms, such as fatigue or pain. Modifying diet and practicing good sleep hygiene are crucial. Starting a rehabilitation exercise program is important. Behavioral modification techniques and stress management may also be used.
• Myofascial pain syndrome
  • Fibromyalgia and myofascial pain syndrome may coexist, creating a complex clinical picture. However, fibromyalgia and myofascial pain syndrome are not the same condition. Some authors assert that fibromyalgia and myofascial pain syndrome can magnify and perpetuate the symptoms of the other.
  • Fibromyalgia is a generalized amplification of pain or hypersensitivity condition associated with tender points in the muscles. These points are exquisitely tender and painful to compression where the pressure is applied; the pain is not referred to distant areas.
  • Narrowly defined, myofascial pain syndrome is a disorder of trigger points. Similar to tender points, trigger points are discreet areas in muscle tissue and/or its associated fascia that are exquisitely tender to compression; however, pain occurs at the site of the applied pressure and also at a distant site (zone of pain referral). Trigger points are found in taut bands (firm, elongated bands) in muscle fibers and are associated with the local twitch response. This response is an involuntary, transient contraction of the taut bands and can be elicited by snapping or pinching the band.
  • Several differences have been noted between fibromyalgia and myofascial pain syndrome; the Table below lists a few of these differences. A more detailed review of the similarities and differences in the 2 syndromes is found in Acupuncture: Trigger Points and Musculoskeletal Pain, which Baldry, a leading British physician and acupuncturist, wrote in 1993.

• Cognitive dysfunction
• • Cognitive function can be considered the ability to think, reason, image, remember, or learn words. The available research on cognition in fibromyalgia suggests that cognitive actions are faulty. This condition may cause some patients the most disability.
  • The euphemism "fibro-fog" is often used to describe the memory problems and unclear thinking (cognitive dysfunction) that patients with fibromyalgia have. Decades of research have shown elucidated several memory systems: short-term, working, episodic, semantic (predominantly verbal memory), and procedural memory (memory for different skills).
  • Symptoms include confusion and forgetfulness, inability to concentrate and recall simple words and numbers, and transposing words and numbers. Cognitive functions are often so impaired that patients cannot perform the activities of daily living (ADL), getting lost in familiar places or losing the ability to communicate effectively. Patients who work may fear of losing their jobs. Pediatric patients many drop out of school because of their inability to complete their schoolwork.
  • Advances in noninvasive technology have made it possible to visualize the brain. Methods such as single photon emission CT (SPECT) have helped define some of the abnormalities linked to the cognitive dysfunction. SPECT shows decreased blood flow in the right and left caudate nuclei and thalami. Functional MRI (fMRI) can show brain activity by depicting increased blood flow to areas actively engaged in a task. Increased blood flow, and hence increased oxygenation, has different magnetic properties. These properties can be detected and measured on fMRI.
  • CNS imbalances have been linked to cognitive dysfunction. Abnormal levels of neurotransmitters such as substance P, serotonin, dopamine, norepinephrine, and epinephrine may be cause cognitive dysfunction. Neuroendocrine imbalance of the HPA axis may play a role in fibro-fog.
  • The distracting quality of pain may be another possible cause of the cognitive dysfunction. Cognitive performance of patients with fibromyalgia is correlated with their reported level of pain. Researchers are looking at tissue volumes in areas of the brain (hippocampus) that may be damaged by the effects of stress hormones. Others studies have implicated yeast overload, water retention, and glial-cell abnormalities as causes of cognitive dysfunction in fibromyalgia.
  • One study showed that the working memory and episodic memory scores of patients with fibromyalgia were similar to those of healthy control subjects who were 20 years older. Patients were matched for age and education.
  • In another study, brain fMRI was performed while participants were shown a string of 3 or 4 letters. These letters were presented in jumbled, nonalphabetical order and then in a maintenance condition in which they alphabetized. The subjects were asked to mentally organize the letters into alphabetical order and then press one key if they were in correct order or another key if they were not. Patients with fibromyalgia performed almost as well as controls, but they activated more brain areas than the controls during the memory task because the task was harder for them to perform. This finding was consistent with results in adults older than the patients.
  • Additional research is needed to determine the brain systems involved, why patients have cognitive problems, and what to do about these problems.

Physical

The goal of the physical examination is to confirm the diagnosis, rule out concomitant systemic diseases, and recognize common coexisting conditions.

The physical examination can be quickly summarized as follows: Palpate the muscles by using 4 kg of pressure. To meet the diagnostic criteria, pain must occur in 11 of 18 paired tender points. The tender-point examination should be performed first during physical examination because a number of factors may influence the sensitivity of the tender points during the examination.

The diagnostic criteria include 2 basic requirements. The first diagnostic criterion is the presence of pain in all 4 quadrants of the body and in the axial skeleton on a more-or-less continuous basis for at least 3 months. The pain often is described as widespread or global. The second diagnostic criterion is the presence of at least 11 of 18 anatomically specific tender points. A tender point hurts only at the area where pressure (enough to cause the examiner's nail bed to blanch, or about 4 kg) is applied, and the patient has no referred pain.

• Procedure for tender-point examination: The thumb pad of the examiner's dominant hand is used to apply pressure to the evaluation sites during the tender-point examination. This allows the examiner to use of important tactile cues and is as reliable as use of a dolorimeter. An instrument known as a dolorimeter can be used to apply exactly 4 kg of pressure over the tender points during the examination. Because the sequence in which the sites are examined may influence the patient's responses, a standardized procedure for evaluating the tender points enhances interobserver reproducibility and reliability in reporting the findings.
• • First, visually locate the evaluation site.
  • Then, with the thumb pad press perpendicularly into the evaluation site for 4 seconds.
  • Press the site only once to avoid sensitization.
  • Four kilograms of pressure should be applied to the site and is enough force to blanch the examiner's nail bed.
  • Have the patient wear a standard gown to allow for easy access to the evaluation sites.
  • Always examine the 18 diagnostic sites and 3 control sites (sites 1,16, and 17; see Site locations below) in the designated order. The 3 control points should be palpated and recorded to provide baseline documentation of the patient's pain perception.
  • Examine the right site then the corresponding left site.
  • The patient should sit on the examination table for evaluation of the first 17 sites. They should lie on his or her side contralateral to the site to be tested for sites 18 and 19, and they should lie on their back for sites 20 and 21.
  • Other tender points may be present and also should be recorded, but they are not necessary for diagnosis. Some patients may present with fewer than 11 tender points. Experts contend that fibromyalgia can be diagnosed with as few as 8 or 9 tender points if the patient has other symptoms, such as sleep problems, fatigue, and any of the characteristic coexisting conditions.
  • The patient should respond with a "yes" or "no" if they have any pain at the site being examined. If the patient's response is "yes," have them rate the pain on a scale of 0 (no pain) to 10 (worst pain), and record each response.
  • The patient's position during examination, the amount of force applied at the evaluation site, the number of times the evaluation site is palpated, and the method of applying force (dolorimeter vs finger pad) may influence tender-point sensitivity.
• Site locations: The 18 possible tender points exist as 9 pairs. Tender points may be found in any palpable muscle, but 18 sites are consistently present in patients with fibromyalgia and are used for diagnosis. The ACR criteria describe 4 pairs of tender points on the anterior of the body and 5 pairs on the posterior of the body.
• • 1, control site = Forehead
  • 2 and 3 diagnostic sites = Occiput at the nuchal ridge
  • 4 and 5 diagnostic sites = Trapezius
  • 6 and 7 diagnostic sites = Supraspinatus
  • 8 and 9 diagnostic sites = Gluteal
  • 10 and 11 diagnostic sites = Low Cervical
  • 12 and 13 diagnostic sites = Second rib
  • 14 and 15 diagnostic sites = Lateral epicondyle
  • 16, control site = Distal middle third of the right forearm
  • 17, control site = Nail of the left thumb
  • 18 and 19 diagnostic sites = Greater trochanter
  • 20 and 21 diagnostic sites = Medial knee
• The 1990 ACR criteria for the location of tender points are as follows:
• • Anterior body - Bilateral
  • • At the fifth through seventh intertransverse spaces of the cervical spine
    • In the pectoral muscle at the second costochondral junctions
    • Approximately 3 finger breadths (2 cm) below the lateral epicondyle
    • At the medial fat pad proximal to the joint line
  • Posterior body - Bilateral
  • • At the upper border of the shoulder in the trapezius muscle midway from the neck to the shoulder joint
    • At the upper border of the shoulder in the trapezius muscle midway from the neck to the shoulder joint
    • At the craniomedial border of the scapula at the origin of the supraspinatus
    • In the upper outer quadrant of the gluteus medius
    • Just posterior to the prominence of the greater trochanter at the piriformis insertion
• Other evaluations: After completing the tender point examination, the physician should include neurologic, joint, and musculoskeletal evaluations. Note the presence of swelling, deformities, and erythema. Examine the patient's gait, joint range of motion (ROM), and posture for structural asymmetry and skeletal deficiencies. Palpate the soft issues for tone or spasm. Check for taut bands, twitch responses, and trigger points; their presence signals the coexistence of a myofascial pain syndrome.

Causes

No cause for fibromyalgia has been accepted universally, though many theories have been proposed. Some authors suggest that an inheritance factor may be involved.

• The frequent comorbidity of fibromyalgia with mood disorders suggests a major role for the stress response and for neuroendocrine abnormalities.
• Fibromyalgia is associated with polymorphisms in the catechol-O-methyltransferase enzyme that inactivates catecholamines and the serotonin transporter gene.
• Basal and stimulated activity of several neuroendocrine axes are altered, and dysfunction of the autonomic nervous system is demonstrated in fibromyalgia.
• Psychosocial factors contribute to the expression of fibromyalgia.
• The question remains: Are these abnormalities causes or effects? Ongoing research may soon provide this answer.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• No tests accurately identify fibromyalgia.
• A new blood test involving antipolymer antibodies was developed.
• • These antibodies are present in approximately 50% of people with fibromyalgia.
  • This biologic marker may provide conclusive evidence for a subgroup of people with fibromyalgia.
• Routine laboratory studies and radiographs are helpful in ruling out other diseases or in diagnosing coexisting conditions.

Imaging Studies

• Some investigators state that imaging studies are helpful only in ruling out other diseases or diagnosing coexisting conditions.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Rehabilitation Program

Physical Therapy

Some investigators believe that a successful rehabilitation program involves a multidisciplinary team of professionals and various modalities individualized for each patient. The team includes the physician, a medical psychologist, physical and massage therapists, and an exercise physiologist. These professionals should have expertise in the treatment of soft tissue disorders.

Traditional therapy or rehabilitation may worsen the patient's symptoms. Monitor the progress of the patient in rehabilitation. As goals are met and symptoms change, modify the rehabilitation prescription to meet the current needs.

• A number of randomized controlled trials of multidisciplinary treatment and exercise combined with education, cognitive behavioral therapy, or both showed that patients had improvements on a 6-minute walk with significant decreases in pain and beneficial efficacy. One randomized controlled trial of multidisciplinary rehabilitation showed improvement in health-related outcomes in a nonclinical, community-based setting at 15-month follow-up. A recently published study evaluated the impact of a physical therapy–based educational program on patients with fibromyalgia and found that the program had a positive impact on the patients' well-being. The study found that the program had no effect on the other symptoms of fibromyalgia.
• Numerous modalities can reduce pain; these include including electrotherapy, cryotherapy, and therapeutic heat. Teach patients how and when to use therapeutic modalities as part of their maintenance program. One investigator recommends muscle energy treatments, positional release methods, and massage as part of the rehabilitation program to decrease stiffness and pain.
• Some investigators have found that daily aerobic and flexibility exercises are an essential component of the rehabilitation program. Exercise was first recognized to have therapeutic benefits 20 years ago. At that time, patients were randomized to receive 20 weeks of high-intensity exercise or flexibility training. Improvements in fitness, global assessment ratings, and tender-point pain thresholds were greater in the high-intensity group than in the flexibility group. Subsequent clinical trials have confirmed the benefits of aerobic exercise and muscle strengthening on mood and physical functioning.
• Patients should begin with gentle warm-up, flexibility exercises and progress to stretching all the major muscle groups. Low-impact aerobic exercise is necessary at least 3 times weekly. Patients should always start at low levels of exercise and progress slowly. The goal is to exercise safely without increased pain. The patients' target exercise regimen is 4-5 times a week for at least 20-30 minutes each time; this may take the patient months to achieve.
• Some patients never may be able to achieve this level of exercise; encourage them to exercise at the highest level possible without worsening their symptoms. Some investigators believe that aquatic exercise may be the safest and gentlest aerobic conditioning exercise available for this group. Aquatic therapy enables aerobic conditioning and also flexibility, strengthening, and stretching exercise. Aquatic exercise is well tolerated and especially helpful for some patients.

Other Treatment

Trigger-point injection is an important technique to provide mechanical disruption (myolysis) of the trigger point. Disruption leads to reduction of pain and an increase in ROM, exercise tolerance, and circulation. Therefore, trigger-point injection is a valuable tool in the treatment of patients with tender points and trigger points. Long-term outcomes improve when these injections are used in conjunction with physical therapy, massage therapy, or stretching exercises done at home.

Both dry needling and needling with infiltration are effective in eliminating trigger points and tender points. Many authors report that needling with infiltration is most effective. Patients with fibromyalgia who receive trigger-point injections have had significant improvement in pain intensity, pain threshold, and ROM. Patients may have delayed improvement in pain but an immediate improvement in ROM. They may also experience severe soreness that develops soon and last long after injection.

• A number of materials and techniques are used for needling with infiltration. Most physicians prefer 1% lidocaine without epinephrine or 0.5% procaine. Lidocaine is often chosen over procaine because it has fewer allergic reactions, a faster onset of action, and greater potency. Steroids are generally not indicated or recommended for trigger-point injections in patients with fibromyalgia. Sterile saline can be used in patients who are allergic to local anesthetics.
• When performing a trigger-point injection, use a sufficiently long needle. In most cases, an extensive area must be infiltrated; therefore, a relatively large volume of 2-12 mL is injected. Before injecting the local anesthetic, make certain that the needle is in the trigger point. Localization of the trigger point is ascertained when the needle either causes a marked increase in pain with referral pain, a fasciculation is seen or felt, or both.
• Several contraindications to trigger-point injections must be observed. Avoid giving these injections in patients with local or systemic infection. Patients with bleeding disorders or those who are taking anticoagulation medication should not receive trigger-point injections without proper medical evaluation, and they should receive these injection only after the risks and benefits are explained clearly to them.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Patients with fibromyalgia have difficulty in tolerating regular doses of most medications and supplements. They are sensitive to medications, and adverse effects are common. To avoid these problems, use the lowest dose available or perhaps one half to one quarter the lowest recommended dose.

Several medications should be avoided or used carefully. To date, the U.S. Food and Drug Administration has not approved any drug for the specific treatment of fibromyalgia.

Avoid complications and confusion by providing written instructions and drug information. These instructions need to be easy to understand. Patients should be instructed to consult their physicians before starting any over-the-counter (OTC) medications or supplements to avoid potentially harmful drug interactions.

Classes of drugs

Most investigators recommend using narcotics sparingly. In fibromyalgia without concomitant rheumatic illnesses, steroids are not helpful and should be avoided.

CNS agents, antidepressants, muscle relaxants, or anticonvulsants, are the most successful pharmacotherapies. These medications affect serotonin, substance P, norepinephrine, and other neurochemicals that have a broad range of activities in the brain and spinal cord, including modulation of pain sensation and tolerance.

Nonsteroidal anti-inflammatory drugs have not been shown to be effective analgesics when used alone, but when combined with tricyclic agents, may be useful as analgesics. Guaifenesin had significant benefits in decreasing pain, improving other symptoms, or laboratory measures in a 12-month randomized controlled study.

Data from randomized controlled trials have not supported the use of thyroid hormones, melatonin, calcitonin, or dehydroepiandrosterone in the treatment of fibromyalgia.

Medications to improve sleep

An effective medication to improve sleep-onset problems is Zolpidem. The patient must be given instructions on proper dosing.

Sleep-maintenance disorders are more difficult to manage than sleep onset. In general, antidepressants are most commonly used because of their effect on serotonin. Tricyclic antidepressants have the strongest evidence for efficacy. The criterion standard is amitriptyline, but many patients cannot tolerate this drug.

Trazodone is an inexpensive, well-tolerated, and effective. The starting dose is 25 mg, and it should be taken at 8 pm. The dose can be slowly up-titrated, if needed. If the patient is not staying asleep, adding a serotonin-selective reuptake inhibitor (SSRI) may be helpful.

Clonazepam may be the drug of choice, if the patient has concomitant restless-legs syndrome or mitral valve prolapse. The starting dose is 0.125 or 0.25 mg taken at 8 pm; titrate the dose to the lowest effective dose.

Tiagabine increases sleep efficiency with a marked increase in slow-wave sleep in health elderly patients. Tiagabine titrated from 2 mg to 12 mg may improve sleep maintenance in some patients.

Gabapentin is being studied. It may also aid in sleep maintenance.

In 1998, pramipexole was described as an excellent treatment for restless-legs syndrome. At the 2000 ACR meeting in Philadelphia, the use of pramipexole at bedtime to treat fibromyalgia was first reported. This medication may aid in sleep maintenance in patients with fibromyalgia and restless-legs syndrome.

Summary

Medications useful for treating fibromyalgia include the following:

• Sleep problems
• • Antidepressants (eg, trazodone, SSRIs, dual-reuptake inhibitors [SNRIs], tricyclic antidepressants)
  • Anticonvulsants (eg, clonazepam, gabapentin, tiagabine)
  • Nonbenzodiazepine hypnotics (eg, zolpidem, zaleplon, eszopiclone)
  • Muscle relaxants (eg, cyclobenzaprine, tizanidine)
  • Dopamine agonists (eg, pramipexole)
• Depression - Antidepressants
• Pain
• • Nonsteroidal anti-inflammatory drugs
  • Muscle relaxants
  • Analgesics (eg, tramadol)
• Other
• • Vitamins and minerals
  • Malic acid and magnesium combination
  • Antioxidants
  • Amino acids
  • Herbs and supplements

Drug Category: Antidepressants

These drugs are used not only to treat depression but also to improve sleep and pain. Antidepressants increase CNS serotonin. Delta-wave sleep also improves. The end result is an improvement of the symptoms experienced by patients with fibromyalgia.

Drug Category: Anticonvulsants

Used to manage pain and provide sedation in patients with neuropathic pain.

Drug Category: Muscle Relaxant

These agents are helpful in the management of muscle spasm and rehabilitation measures.

Drug Category: Nonbenzodiazepine Hypnotics

Indicated for insomnia.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Inpatient Care

• The rehabilitation program is incomplete without psychological intervention.
• Many patients with fibromyalgia have increased levels of stress and feelings of depression, anxiety, and frustration.
• Several treatment options are available. According to Buckelew, cognitive behavioral therapy, relaxation training, group therapy, biofeedback, and stress management are some of the most useful options.
• Buckelew et al found that patients receiving aerobic training plus biofeedback had significant improvements in tender-point pain, self-reported physical function, and self-efficacy for function, as compared with a control group.

Further Outpatient Care

• Cognitive behavioral therapy (CBT) techniques emphasize changes in thought patterns and behaviors. CBT can be performed in a one-on-one or group setting with beneficial effects achievable in as few as 10 sessions. These techniques have been used in chronic pain treatment programs that manage patients with fibromyalgia. A recent study reviewed the results of 13 programs using CBT. Generally, CBT provided improvements in pain-related behaviors, coping strategies, and overall physical function; however, providing CBT alone is not advantageous over group programs of exercise or education or both.

Complications

• Symptoms of fibromyalgia vary.
• • Patients may experience few symptoms one day and many the next.
  • Some investigators describe a flare-up as a time when the patient experiences an acute intense increase in symptoms that last more than a day. The pain may be amplified to such intense levels that the patient becomes bedridden.
  • Flares-ups usually are triggered by a stressor. The stressor may be infection, trauma, or changes in medication, sleep, or exercise. Onset of allergies, changes in diet, and a change in usual activity may bring on a flare-up.
  • Teach patients about the triggers of flare-ups. On occasion, no trigger can be identified. Patients must learn to identify their triggers and what measures to take to decrease their symptoms.
• Some tips for avoiding an