Course Authors

M. Nergis Alnigenis (Yanmaz), M.D., and Peter Barland, M.D.

Dr. Alnigenis is a Visiting Fellow in the Division of Rheumatology, Montefiore Medical Center. Drs. Alnigenis and Barland report no commercial conflict of interest.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 

Learning Objectives

Upon completion of this Cyberounds^®, you should be able to:

• Describe the major clinical manifestation of FMS

• Discuss the diagnostic criteria for FMS and differential diagnosis

• List the treatment options for FMS.

 

Fibromyalgia syndrome (FMS) is a commonly encountered syndrome characterized by diffuse persistent musculoskeletal pain, stiffness, tenderness, sleep disturbance and easy fatigability, affecting predominantly women.

Epidemiology

In the early studies of prevalence, which employed modifications of the currently accepted diagnostic criteria, the proportion of patients in rheumatology clinics with FMS has been reported as 10% to 20%, while in nonspecialized settings, the reported prevalence was 2.1% to 5.7%.(1) Initial population-based studies in Sweden and Norway reported that 1-2% of all randomly selected individuals have FMS.(2),(3) A recent population-based study in North America, using the American College of Rheumatology (ACR) 1990 criteria for the classification of fibromyalgia, estimated the prevalence as 2% for both sexes, 3.4% for women and 0.5% for men.(4),(5)

The syndrome is reportedly the second most common problem seen by rheumatologists in North America and is recognized as a major source of disability in some European countries and in North America.(6),(7)

The typical patient with FMS is a woman (80 to 90% of the patients) and the mean age varies from 30 to 60 years in different studies.(8) In a study by Wolfe et al., the prevalence of FMS increased with age and highest values were attained between 60 and 80 years (reaching 7% in women at this age group).

Clinical Features

Patients with FMS often attribute an "event" to the onset of their symptoms. Events that most commonly have been linked to the precipitation of FMS are shown in Table 1.

The cardinal symptom of FMS is chronic widespread pain, most often involving contiguous regions. Generally, the patient states that "it hurts all over" and has difficulty locating the site of the pain arising from articular and non-articular tissues. Pain in FMS typically waxes and wanes in intensity. Flares are associated with unaccustomed exertion, soft tissue injury, lack of sleep, cold and stress.(9)

Most FMS patients also report profound fatigue. This is often notable when arising from sleep but also is marked in the mid-afternoon. Seemingly minor activities aggravate the pain and fatigue, although prolonged inactivity also heightens the symptoms. Patients are stiff in the morning and feel unrefreshed, even if they have slept 8 to 10 hours. Many patients do not report sleep disturbances. Nevertheless, they usually recognize that they sleep lightly, waking frequently. Signs and symptoms, other than pain, fatigue and tenderness, are shown in Table 2.(9)

Modified from Wolfe F, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 Criteria for the classification of fibromyalgia: Report of the Multicenter Criteria Committee. Arthritis Rheum 33:160-172, 1990: with permission.

Tenderness is the feature that most readily allows separation of FMS from other disorders that produce widespread pain. Tender point sites represent specific areas of muscle, tendon, fat pads or bursal regions that are much more tender (painful) to palpation than the surrounding sites. Patients, in general, are not often aware of the location of many of the tender points. Trigger points are self-sustaining, hyperirritable foci located in skeletal muscle or its associated fascia and have taut bands of muscle that produce pain, referred pain and a local twitch response when pressure is applied.(11) Figure 1 shows the 18 tender point sites of the 1990 ACR criteria for the classification of FMS.

Figure 1. Eighteen Tender Point Sites of FMS.

Tender points can be elicited and measured by two methods: digital palpation and dolorimetry. To test for pain with digital palpation, the examiner presses the tender-point site with an approximate force of 4kg. Usually, the second and third fingers or the thumb are used for palpation, applying pressure to the point when the fingernail bed begins to blanch. The patient is asked for the presence of the pain.

Dolorimetry, or pressure algometry (Figure 2), is a technique whereby a rubber endplate, attached to a spring-loaded force gauge, is pressed onto the tender-point site. Patients are asked to state when the pressure is noted to change from pressure to pain. A value equal to or less than 4kg/1.77cm(2) has been used as approximately equivalent to a positive tender point. Dolorimetry accuracy for diagnosis is 73.1%, compared to 84.2% for digital palpation in the ACR criteria study.(5)

Figure 2. Pressure Threshold Meter.

Control anatomic sites, such as over the thumbnail, mid-forearm and forehead should also be palpated and are often not as painful as the previously mentioned anatomic sites. In a recent study by Wolfe et al., however, positive control points were common (63%) in FMS. In this study, the paired left and right third finger at the midpoint between proximal and distal interphalangeal joint and the paired left, and right quadriceps about 10cm proximal to the patella were used as control points.(12)

On physical examination, patients with primary FMS usually appear well with no obvious systemic illness or articular abnormalities. A neurological examination usually does not demonstrate any significant abnormality.

Laboratory and radiological investigations in FMS are largely unrevealing and primarily useful in searching for the presence of concomitant disorders and the disorders in the differential diagnosis of FMS.

Relationship of Fibromyalgia to Other Systemic Disorders

FMS has been shown to coexist with many rheumatic and nonrheumatic diseases (concomitant diseases [See Table 3]). When the syndrome is associated with a concomitant disease, it is classified as secondary FMS. However, the 1990 ACR criteria for the classification of FMS suggest abolishing the distinction between primary and secondary forms and recommends diagnosing FMS in any case meeting the criteria.(5)

Certain rheumatic and nonrheumatic diseases can also mimic FMS, initially with similar complaints, mostly pain and fatigue, and must be considered in the differential diagnosis (Table 4). The FMS symptoms for patients who have a systemic illness, in association with their FMS, improve when they receive treatment for their underlying disease.

Fibromyalgia patients often have a variety of overlapping conditions or syndromes. They are shown in the Table 5.

Laboratory methods that are used to rule out other possible diagnoses are shown in Table 6.

When to Diagnose FMS?

Various diagnostic criteria in the past were suggested to diagnose FMS. Each is based on the exclusion of rheumatic or systemic diseases and the presence of certain symptoms and tender points. Authors have debated the optimal number of tender points, as well as the relevance of the concept of primary and secondary FMS. Subsequently, a North America multicenter criteria committee developed ACR 1990 criteria for the classification of FMS (Table 7).(5) The criteria yielded a sensitivity of 88.4% and specificity of 81.1%.(5) There was no significant difference in patients considered to have primary/concomitant vs. secondary FMS and for classification purposes such distinctions were discarded. Patients meeting those criteria can also have many of the other symptoms listed in the Table 2. These criteria have been increasingly used in rheumatology practices, and in clinical and epidemiological studies.

Digital palapation should be performed with an approximate force of 4kg. A tender point has to be painful at palpation not just "tender."

Psychiatric and Psychosocial Aspects of FMS

There is still some dispute as to whether FMS should be regarded as a somatic illness or as a psychiatric disorder. In the past, FMS was often considered a manifestation of psychogenic rheumatism and patients were felt to be hysterical. Patients with FMS look well and have normal laboratory tests and "subjective" pain related measures are utilized for diagnosis. Many of the symptoms seen in FMS can also occur in depression and in other psychiatric conditions. Investigations, including muscle biopsy and nuclear magnetic resonance spectroscopic studies, have all proved inconclusive and studies of psychiatric symptoms in patients with FMS have shown varying and conflicting results. Methodological problems, however, are frequently encountered in such studies.(13)

Chronic pain is known to be associated with anxiety, as well as with depression, and clinical depression is often associated with fatigue, sleep disturbances and, sometimes, pain, but discrete tender points do not occur. In FMS, depression is typically a continuous problem from its onset and, despite resolution of depression, the symptoms of FMS persist.(14) Walker et al.(15) reported that, when compared to the rheumatoid arthritis patients, those with FMS had significantly higher lifetime prevalence rates of all psychiatric diagnosis and nearly all the FMS patients had at least one lifetime diagnosis, as well as higher mean numbers of medically unexplained physical symptoms.

Some researchers consider FMS as a somatic disorder because of the polysymptomatic nature of FMS and its similarities to DSM-IV criteria for somatic disorder.(14) Some have even suggested it as being a factitious disorder.(14) In a study on childhood experience of maltreatment in FMS patients, they had, significantly, higher lifetime prevalence of all kinds of victimization.(16)

In summary, although empirical evidence for the psychological basis of FMS remains elusive, psychological function may be important in establishing and maintaining this disorder.

Widespread Pain and Tender Points in General Population

FMS may represent a clinically important stage of widespread musculoskeletal pain continuum in the population, rather than a discrete disease.

In a study by Wolfe et al. in Wichita, Kansas, chronic widespread pain was present in 10.6% of the population studied and prevalence of chronic regional pain was 20.1%.(4) In this study, rates were generally much higher for women than for men and were almost two times higher in age group 50 to 69.(4) By the age 60, more than 50% of women and almost 40% of men had some form of musculoskeletal pain.(4)

Croft et al. reported the point prevalence of chronic widespread pain as 11.2%.(17) In this study, most of the patients with chronic widespread pain (60%) had fewer than 11 tender points. In contrast, 19% of the patients with regional pain and 5.1% of controls without pain had more than 11 tender points. Women had a higher median tender point count (six) than men (three). In the population studied, only 18 of 38 cases with a high tender point count (>11 tender points) had chronic widespread pain. Tender points were associated with pain but were separately related to other measures of distress, namely, depression, fatigue and, in particular, poor sleep. It was concluded that FMS was not a distinct entity in the general population.

Pathophysiology

Several pathophysiological mechanisms have been proposed for FMS. A summary of suggested mechanisms is shown in the Table 8. None of those mechanisms is widely accepted or proven by rigorous scientific methodology.

Management(19),(20)

Management of FMS must be multifaceted and include combinations of pharmacological and nonmedicinal modalities. Therapy must directed to symptoms and individualized. The patient must be allowed to take charge of his/her therapy and develop coping skills. Recommended modalities include:

1. Treatment of concomitant or overlapping disorders.
2. Control modulating factors (barometer changes, humidity, cold, warmth, noise etc.).
3. Lifestyle modifications: healthy diet, regular exercise, work modifications, preventive medicine.
4. Managing pain: non-narcotic analgesics (acetaminophen, tramadol), heat and cold treatments. Narcotic analgesics should be used sparingly and for a defined period, only under special circumstances.
5. Improving sleep quality: analysis of sleep, treating sleep disturbances (sleep apnea, restless leg syndrome), improving sleep hygiene, medications (zolpidem tartrate).
6. Dealing with fatigue: optimizing rest and activity, pacing yourself.
7. Medications:
   1. Nonsteroidal anti-inflammatory drugs (NSAIDs): When used alone, they are not effective.
   2. Tricyclic antidepressants (TCAD): amitriptyline (2.5-50mg PM /2-3 hours before bedtime), cyclobenzaprine (10-30mg PM), doxepin, nortriptyline, trazodone. TCAD can decrease depression, relax muscles, improve sleep and release endorphins. Some patients may develop weight gain, constipation, orthostatic hypotension, agitation and morning hangover. In general, clinical trials indicate the superiority of both amitriptyline and cyclobenzaprine to placebo in producing subjective improvement in pain (significant but modest), sleep quality and fatigue. These effects may appear in four weeks of treatment but tend to wane over time. Only amitriptyline reduces patients' tender points. This class of drugs produces a meaningful improvement in about 30% to 50% of patients.
   3. Serotonin reuptake inhibitors: fluoxetine (10-20mg AM), sertraline (50-200mg AM), paroxetine (5-20 mg AM),nefazodone, venlafaxine. In combination with TCAD drugs (after several weeks they can be added), morning administration of these drugs may improve daytime fatigue and decrease pain. Fluoxetine together with amitriptyline was found more effective than placebo in reducing FMS symptoms, and combination of both worked better than either alone. Fluoxetine alone, however, does not produce beneficial effect; neither does citalopram, tenoxicam and bromazepam.
   4. Muscle relaxants: cyclobenzaprine. They may be helpful in combination with amitriptyline.
   5. Benzodiazepins: clonazepam (0.5-1mg PM), alprazolam (0.25-1.5mg PM). They promote improved sleep, relax the muscles and help restless leg syndrome. In a clinical trial, treatment with alprazolam combined with ibuprofen demonstrated modest improvement.
   6. Local injections with lidocaine and steroids.
   7. Topical creams: capsaicin 0.25%. (3 to 4 times a day). The patient should be cautioned that this topical cream can irritate the eyes.
   8. Others: NSAIDs alone and corticosteroids, magnesium and malic acid, bright light, S-adenosyl-L-methionine alone and topical lidocaine hydrochloride in sphenopalatine blocks were not found effective in the management of FMS.
8. Physical therapy, in the forms of EMG-biofeedback, acupuncture, hypnosis has shown some benefit in controlled trials. Exercise programs include aerobic exercises (low impact exercises; brisk walking, biking, swimming, water aerobics), strengthening and stretching exercises. Aerobic exercise programs have been found more effective than simple relaxation or stretching in some trials. Enhanced cardiovascular fitness was achieved and sustained during these trials. EMG-biofeedback, hypnotherapy and electroacupuncture have also been shown to have some efficacy in the treatment of FMS.
9. Dealing with stress, depression and specific psychologic problems such as, alcoholism and childhood abuse. Modalities include cognitive behavioral therapy, counseling, relaxation techniques, self-help groups. In clinical studies cognitive behavior therapy has been proved an effective tool in FMS.
10. Patient education. The patient must be informed that this disorder is neither life threatening nor imaginary nor associated with development of joint deformities. Educational literature from Arthritis or Fibromyalgia Societies should be supplied. Access to support groups or services can reduce patient anxiety and constitutes an important part of management (see the list of fibromyalgia sites on the Internet below).

Fibromyalgia Network

Oregon Fibromyalgia Foundation

National Fibromyalgia Research Association