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Comprehensive Assessment of Fibromyalgia and Overlapping Conditions

  • Authors: Don L .Goldenberg, MD
  • CME/CE Released: 5/28/2010
  • Valid for credit through: 5/28/2011
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Target Audience and Goal Statement

This activity is intended for rheumatologists, primary care providers, neurologists, psychiatrists, and nurses.

The goal of this activity is to examine the prevalence of fibromyalgia, identify its key presenting features, and improve fibromyalgia patient assessment.

Upon completion of this activity, participants will be able to:

  1. Recognize the prevalence of fibromyalgia and the impact of failure to treat
  2. Identify key presenting features of fibromyalgia
  3. Develop an approach to fibromyalgia patient assessment in the clinical setting based on latest insights and tools
  4. Recognize other diseases that may mimic fibromyalgia and understand how to assess a patient to rule out overlapping conditions


The Accreditation Council for Continuing Medical Education and the Association of American Colleges have standards and guidelines to ensure that individuals participating in CME activities are aware of relationships between authors and commercial companies that could potentially affect the information presented. The University of Michigan Medical School follows these national policies to ensure balance, independence, objectivity, and scientific rigor in all its CME activities. Each author was asked to complete a disclosure information form for this activity. Disclosures are reported below.


  • Don L. Goldenberg, MD

    Professor of Medicine, Tufts Medical School, Boston, Massachusetts; Chief of Rheumatology, Newton-Wellesley Hospital, Newton, Massachusetts


    Disclosure: Don L .Goldenberg, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Forest Laboratories, Inc.; Pfizer Inc.; Eli Lilly and Company
    Received grants for clinical research from: Forest Laboratories, Inc.

    Dr. Goldenberg does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics not approved by the US Food and Drug Administration (FDA) for use in the United States.

    Dr. Goldenberg does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.


  • Florencia Schapiro, PhD

    Scientific Director, Medscape, LLC


    Disclosure: Florencia Schapiro, PhD, has disclosed no relevant financial relationships.

CME Content Reviewer

  • Daniel J. Clauw, MD

    Professor of Medicine, Division of Rheumatology, University of Michigan, Ann Arbor


    Daniel J. Clauw, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Pfizer Inc.; Eli Lilly and Company; Cypress Bioscience, Inc.; Pierre Fabre Pharmaceuticals Inc.; UCB Pharma, Inc.; AstraZeneca Pharmaceuticals LP.
    Received grants for clinical research from: Pfizer Inc.; Forest Laboratories, Inc.

    Dr. Clauw does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics not approved by the US Food and Drug Administration (FDA) for use in the United States.

    Dr. Clauw does intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.

CME Reviewer/Nurse Planner

  • Laurie E. Scudder, DNP, NP

    Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland


    Disclosure: Laurie E. Scudder, DNP, NP, has disclosed no relevant financial relationships.

Accreditation Statements

This activity is sponsored by the University of Michigan Medical School in partnership with the National Fibromyalgia Association, and Medscape, LLC.

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  • The University of Michigan Medical School is responsible for the content, quality, and scientific integrity of this CME activity.

    This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the University of Michigan Medical School and the National Fibromyalgia Association. The University of Michigan Medical School is accredited by the Accreditation Council for continuing Medical Education (ACCME) to provide continuing medical education for physicians. The University of Michigan Medical School designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

    Estimated time to complete: 1.0 hour

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Comprehensive Assessment of Fibromyalgia and Overlapping Conditions: Would Other Physical Findings Be Useful in the Differential Diagnosis?


Would Other Physical Findings Be Useful in the Differential Diagnosis?

The longer CWP and exhaustion are present without abnormal findings on physical examination and routine laboratory testing, the more likely that fibromyalgia is the correct diagnosis. During the first few months, however, other diseases may mimic fibromyalgia. Whereas certain symptoms, such as fever, murmur, weight loss, and elevated ESR or CRP levels, are never present in fibromyalgia, several symptoms do overlap with those of other conditions (Table 2).

Table 2. Differential Diagnosis of Fibromyalgia

Condition Distinguishing Features Special Diagnostic Issues
Viral illness Fever, rash, abnormal laboratory results Self-limited
Rheumatoid arthritis Small joint polyarthritis, elevated ESR Often concurrent with fibromyalgia
Systemic lupus erythematosus Rash, multisystem inflammation, elevated ESR, ANA levels, and anti-DNA antibody levels Often concurrent with fibromyalgia
Polymyalgia rheumatica Age ≥ 60 years, severe stiffness, less pain, elevated ESR Normal examination; short trial of prednisone may be used; enzymes normal in some patients
Myositis Weakness rather than pain, elevated muscle enzyme levels Enzymes normal in some patients
Spondyloarthropathya Back and neck immobility, elevated ESR, abnormal x-rays/imaging findings No obvious synovitis
Neuropathies Weakness, loss of sensation, abnormal results on electromyography and nerve conduction velocity test Neurologic abnormalities in fibromyalgia (?)
ANA = antinuclear antibody; ESR = erythrocyte sedimentation rate
aSeronegative spondyloarthropathies, including ankylosing spondylitis
From Goldenberg DL. Am J Med. 2009;122:S14-S21.[34] Republished with permission.

Any of the systemic connective tissue diseases may present with fatigue and myalgias before physical and laboratory abnormalities are detected. Such characteristic findings, however, appear soon after the onset of symptoms. In RA, early classic features include small-joint polyarthritis, usually involving the fingers, wrists, and feet, with an elevated ESR or CRP. In SLE, multisystem signs, including rash, fever, and pulmonary, cardiac, and renal manifestations, are often present, in addition to elevated levels of ANA and anti-DNA antibodies, anemia, leukopenia, and thrombocytopenia.

Because fibromyalgia is present in 10%-30% of patients with RA and SLE,[28-31] sometimes it can be difficult to determine whether the pain and fatigue are related to an exacerbation of the systemic connective tissue disease or to concurrent fibromyalgia. This differential issue may be complicated and is best resolved with a comprehensive rheumatology evaluation.

Polymyalgia rheumatica (PMR), a condition that usually affects individuals over age 60 years, is not usually associated with abnormal physical findings and causes fatigue and generalized myalgias that can mimic fibromyalgia. Typically, however, PMR causes more severe stiffness than widespread pain and is commonly linked to elevated ESR or CRP. In older patients, when it is difficult to differentiate PMR from fibromyalgia, a few weeks trial of 10-20 mg of daily prednisone may be justified. Although corticosteroids are not effective in fibromyalgia, patients with PMR would exhibit a dramatic response that includes normalization of ESR and CRP levels.

Ankylosing spondylitis or other of the seronegative spondyloarthropathies may be misdiagnosed as fibromyalgia. Typically, however, these conditions are not characterized by peripheral joint arthritis, exhibit more limited back motion, and usually have an insidious onset, with more back pain and stiffness. Abnormal back and sacroiliac x-rays or imaging findings and elevated ESR or CRP levels are useful in making the correct diagnosis.

Given that patients with fibromyalgia often report diffuse paresthesias, a localized or systemic neurologic disorder may mimic this condition. Although a number of reports described a high prevalence of subtle neurologic abnormalities among these patients, the neurologic examination is usually unrevealing. A recent study found that patients with fibromyalgia exhibited more neurologic symptoms than did pain-free controls, including abnormalities in cranial nerves IX and X (42% vs 8%, respectively), as well as in sensory (65% vs 25%), motor (33% vs 3%), and gait (28% vs 7%) functions.[32] Patients with fibromyalgia reported significantly more neurologic symptoms than the control group; the greatest differences were for photophobia (70% vs 6%), poor balance (63% vs 4%), and weakness and tingling in the arms or legs (58% vs 2% and 54% vs 4%). Poor balance or coordination, tingling or weakness in the arms or legs, and numbness in any part of the body correlated with appropriate neurologic examination findings in the fibromyalgia group.

A prolonged viral illness, such as infectious mononucleosis, may manifest as chronic fatigue and nonspecific aches and pains. A history of fever, rash, sore throat, and liver or spleen enlargement with suggestive laboratory tests, however, would point toward that diagnosis, not fibromyalgia. Subacute bacterial infections may also cause exhaustion and generalized myalgias.

Comorbid Conditions

Fibromyalgia is closely associated with other functional somatic syndromes, including CFS, IBS, temporomandibular pain disorders, migraine and tension headaches, and painful pelvic and bladder syndromes. These comorbid conditions can add to the diagnostic confusion when evaluating a patient with fibromyalgia. Even though validated diagnostic classification criteria for most of these disorders exist (Table 3),[33] many of their characteristic symptoms (eg, chronic pain, fatigue, sleep, and mood disturbances) are similar to those of fibromyalgia.

Table 3. Screening Questions and Clinical Criteria to Distinguish Fibromyalgia From Other Central Pain Disorders

Condition Question Clinical Criteria
Chronic fatigue syndrome Unexplained, persistent, or relapsing fatigue for ≥ 6 months? Fatigue plus 4 of the following symptoms: (1) short-term memory loss, (2) sore throat, (3) tender lymph nodes in the neck or armpit, (4) muscle pain, (5) joint pain without swelling or redness, (6) headaches, (7) nonrestorative sleep, (8) malaise
Irritable bowel syndrome Abdominal discomfort or pain accompanied or affected by constipation or diarrhea for ≥ 3 months in the past year? Abdominal discomfort/pain with 2 of these features: (1) relief with defecation, (2) onset associated with a change in frequency of stool, (3) onset associated with a change in form of stool
Temporomandibular disorders Recurrent facial/jaw pain and/or limitation in jaw opening occurring in the past 6 months? Pain or tenderness of the temporomandibular joint and/or surrounding muscles, joint noises, and limitation or loss of jaw movement often accompanied by headache or ear pain
Multiple chemical sensitivities Symptoms in multiple organ systems reliably occurring on exposure to multiple unrelated chemicals? Multiple symptoms (eg, pain, fatigue, difficulty concentrating, numbness) in multiple organs upon low-level exposure to multiple chemicals (pesticides, alcohol, solvents) that usually resolves upon removal of agents
Tension/migraine headaches Recurrent headaches (≥ 10 days for tension-type; ≥ 5 days for migraine) lasting 30 minutes occurring in the past 6 months? Migraine: At least 2 of the following characteristics accompanied by nausea/vomiting or photo/phonophobia: (1) unilateral location, (2) pulsating quality, (3) moderate/severe intensity, (4) aggravation by routine physical activity

Tension headache: At least 2 of the following characteristics: (1) pressing/tightening quality, (2) mild/moderate intensity, (3) bilateral location, (4) no aggravation by routine physical activity
Interstitial cystitis Bladder pain, urinary urgency and frequency (voiding > 8 times during the day, > 2 times during the night) for > 9 months, and a negative urine culture? Glomerulations on cystoscopic examination or classic Hunner ulcer and pain associated with bladder or urinary urgency; multiple exclusion criteria
Localized and myofascial pain disorder Localized muscle pain for ≥ 3 months? Trigger points/tender spots in a taut band of skeletal muscle that produce a local twitch response upon palpation and may result in a predicted pain referral pattern
From Goldenberg DL. Am J Med. 2009;122:S14-S21.[34] Republished with permission.

In addition to unexplained exhaustion lasting for more than 6 months, the cardinal feature of CFS, this condition is also characterized by myalgias, joint pain, headaches, and sleep disturbances, which are also common in fibromyalgia. In various studies, 30%-70% of patients with CFS met the ACR criteria for fibromyalgia.[34,35] Abdominal discomfort or pain accompanied or affected by constipation or diarrhea for 3 months or longer are the main diagnostic features of IBS (30%-60% of patients with IBS have fibromyalgia). Temporomandibular joint dysfunction and myofascial pain syndrome are the 2 comorbid conditions that may be the most difficult to distinguish from fibromyalgia. Temporomandibular joint dysfunction is diagnosed in individuals who experience recurrent facial/jaw pain and/or limitation in jaw opening for 6 months. The diagnostic criteria for myofascial pain syndrome, which have not been widely accepted, include chronic localized muscle pain associated with trigger points and/or tender spots in a taut band of skeletal muscle that produce a local twitch response upon palpation and may result in a predicted pain referral pattern. Some clinicians believe that myofascial pain is simply a more focal form of fibromyalgia.[36]

Both CWP and fibromyalgia are strongly associated with mood disturbances, remote and recent adverse life events, and general distress.[37-39] Several studies have demonstrated a significant correlation between psychiatric disorders and fibromyalgia, including an odds ratio of 2-3 for major depression and 3-6 for any anxiety disorder.[40] Overall, patients with fibromyalgia were 2-7 times more likely to have 1 or more comorbid conditions, including depression, anxiety, headache, IBS, and CFS.[16]

The most logical way to think about the overlap of these comorbid conditions and fibromyalgia is to focus on their similarities rather than attempting to split their differences. For diagnostic purposes, clinicians should expect that fibromyalgia is comorbid with CFS, IBS, chronic headaches, and pelvic/bladder pain syndromes. It is probably of little importance to label a patient with 4 or 5 syndrome diagnoses compared with trying to understand their comorbid nature. Instead, symptoms of each of these syndromes in a patient suspected of having fibromyalgia should provide more comfort for that diagnosis.

Why do you need to make a timely and accurate diagnosis? Despite the recognition that fibromyalgia is one of the most common causes of chronic pain, clinicians still argue about whether it is helpful or harmful to make a diagnosis. Some believe that making a diagnosis of fibromyalgia is harmful to patients because it "medicalizes" symptoms that every human being experiences at times. Subsequently, giving a label to symptoms such as pain or fatigue induces illness behavior. This argument, however, can be extended to any common symptom, including headaches and low back pain. Indeed, if an individual believes that fibromyalgia is a specific disease, largely out of their own personal control and caused by some type of external factor, helplessness and hopelessness may become quite prominent.

To prevent this scenario, the diagnosis of fibromyalgia must be integrated with information and education. Fibromyalgia should be explained as a symptom, like migraine headaches or hypertension, with a scale from very mild to more severe. A biopsychological model needs to be introduced, and clinicians should avoid causal inference. Patients should be dissuaded from the concept that they have sustained an injury or an infection as the cause of their chronic pain and exhaustion. With that knowledge in place, most patients will stop doctor-shopping and undergoing numerous unnecessary tests in an attempt to find specific cures or causes for their disease.

When such information is combined with an accurate diagnosis, patients tend to improve. Many studies, especially from the United Kingdom, have demonstrated that once fibromyalgia is diagnosed, fewer referrals, blood tests, and imaging studies are ordered. Some studies have shown a decreased use of medications after an appropriate diagnosis, adding up to cost savings for society.[41]

Unfortunately, most studies of fibromyalgia are conducted in tertiary referral centers and include patients who have had symptoms for 5-8 years. It is therefore unclear whether fibromyalgia presents differently in the community. Evidence, however, suggests that earlier diagnosis of fibromyalgia would significantly improve patient outcome. Hence, an earlier and more timely and efficient diagnosis of fibromyalgia is important (Table 4).[34]

Table 4. Making an Earlier Diagnosis of Fibromyalgia

Rheumatic Illness
"I hurt all over"

"It feels like I always have the flu"

Fatigue, sleep and mood disturbances

Unremarkable examination
Systemic connective tissue disease (RA, myositis, SLE, polymyalgia rheumatica)

Seronegative spondyloarthropathies may be confusing

Fibromyalgia common in RA and SLE
Exclude structural or systemic disease

Do not conduct a "fishing" expedition

Avoid "screening" rheumatology tests

Diagnosis is most efficient with early subspecialty referral

RA = rheumatoid arthritis; SLE = systemic lupus erythematosus
Data from Goldenberg DL. Am J Med. 2009;122:S14-S21.[34]

The accuracy of diagnosing fibromyalgia in primary care is improving. A report from 2003 revealed that primary care doctors made a correct diagnosis in only one third of patients suspected of having fibromyalgia and referred to rheumatologists, often missing seronegative spondyloarthropathies.[42] In contrast, a study of family physicians in 2009 that used a rheumatologist's diagnosis as gold standard found nearly 90% concordance between the rheumatologist's and family doctor's diagnosis among various ethnic groups.[43]

In making an earlier and accurate diagnosis, 2 statements should strongly suggest fibromyalgia: "I hurt all over" and "It feels like I always have the flu". Most patients with fibromyalgia will report fatigue, sleep disturbances, bowel and bladder symptoms, and mood disturbances. The physical examination should be unremarkable other than evidence of hyperalgesia. If the symptoms have been present for months or years, laboratory testing will probably be of very low yield; thus, a "fishing expedition" with "screening" blood tests should be avoided. When there is concern about the presence of a systemic rheumatic disease or neurologic condition, early referral to a specialist is cost-effective (Table 4).

In addition to making an earlier diagnosis, it is important to determine the symptom domains that seem most distressing for each patient, which is where the art of chronic illness management comes to the surface. This stratification might be accomplished by the primary provider or may require subspecialty referral to a physical medicine and rehabilitation specialist, a sleep specialist, or a mental health professional.