CHAPTER 42

Fibromyalgia and Diffuse Illnesses

Karen Anderson Keith, PhD, RN • Robert Keith, MPA, PA-C, CCPA

One of the most puzzling and frustrating problems confronting primary care providers is the evaluation of vague symptoms such as weakness, fatigue, or widespread pain. Often these complaints are self-limiting, and because a complete evaluation would require an in-depth workup, patients may be given a preliminary evaluation and asked to return if the problems persist. If the problems do persist, patients are frequently referred to specialists for evaluation, with variable results. The years following 1995, and particularly since 2010, have provided us with insight into how some of these complaints can be understood and offer practical approaches to their evaluation and management (Stein, 2013). Once considered the purview of specialists, these diagnoses are becoming issues for the primary care clinician, with specialist collaboration/guidance (Arnold, Clauw, Dunegan, & Turk, 2012; Firestone, Holton, Mist, Wright, & Jones, 2012).

This chapter provides a framework for the initial assessment and evaluation of some complex diagnoses often encountered in primary care (fibromyalgia [FM], idiopathic inflammatory myopathies [IIMs], and myasthenia gravis [MG]), three conditions in which the chief complaints are weakness, fatigue, and widespread pain. All typically require at least some pharmacologic intervention and these therapies are mentioned often with specific dosage recommendations. Because treatments evolve, therapeutic suggestions should be considered in the context of the patient, stage of the disease, and current community guidelines. Primary care providers, through a patient-centered approach to care, play an important role in the initial workup, management, and (when indicated) comanagement or referral of patients with diffuse illnesses. Table 42.1 lists these and other diseases that can present with weakness.

DEFINITIONS

Weakness

Weakness is best understood from the patient’s perspective as a functional limitation in the activities of daily living. In this sense, the perceived weakness is limiting the patient’s abilities, but is not elicited upon careful physical examination. The patient does not have the energy to complete the movement or attempting the movement elicits pain; the patient perceives this as weakness. If actual muscle weakness is present, the differential diagnosis includes ascending paralysis, bulbar symptoms, descending paralysis, hemiparesis, monoparesis, paraparesis, tetraparesis, Todd paralysis (postictal states), upper motor neuron lesions, and lower motor neuron lesions (Lucey, 2005).

Fatigue

Fatigue is distinguished from tiredness by its chronic nature, lack of relief with rest, and feeling of lack of energy in body and spirit or ability to perform routine daily tasks. Fatigue is considered persistent if it has been present for more than 6 months (Kaufman, 2010).

Pain

Pain is a universal sensation, though experienced as/by an individual. Pain is conceptually divided into the categories of acute and chronic. Acute pain, a physiological reaction to a negative or dangerous stimulus, provides defensive service to a person. Chronic pain, however, has no clearly known positive outcome and is a cause of significant morbidity in the United States and Canada (Canadian Pain Coalition, n.d.; Institute of Medicine [IOM], 2011; Mayday Fund Special Committee on Pain and the Practice of Medicine, 2009). Experts have noted that the term chronic pain is considered stigmatizing, and is being replaced by the phrase persistent pain (Dahlin, Duffy, & Franciose, 2013).

In general, four types of pain can be recognized. Acute pain is associated with trauma and inflammation and is typical of nociceptive pain. Nociceptive pain is characterized by overstimulation of peripheral pain receptors. In contrast, neuropathic pain is the result of direct injury to nerves. Psychogenic pain is related to psychiatric illness. The final type of pain, and that which is seen in FM, is less well understood; it is typified by chronic pain of complex etiology—in which many interacting hormones, neurotransmitters, cellular, genetic, and biosocial factors contribute to ongoing pain (Buckner Winfield, 2007).

TABLE 42.1

Disorders Presenting With Muscle Weakness

DISORDER	PRESENTATION: MUSCLE WEAKNESS AND OTHER SYMPTOMS
Fibromyalgia	Fatigue, nonrestorative sleep Numbness Chronic, widespread, fluctuating, aching pain Headaches Symptoms of irritable bowel syndrome
Idiopathic inflammatory myopathies Dermatomyositis Polymyositis Inclusion body myositis	Weakness begins in legs, goes to upper extremities and possibly neck May have cutaneous manifestations
Myesthenia gravis	Double vision Asymmetric ptosis Difficulty chewing or swallowing Weakness varies diurnally; improves with rest Waxing and waning course Weak voice Choking Sensation and reflexes normal
Rhabdomyolysis	Muscle pain (selective muscle involvement) History of a crushing injury, alcohol abuse, muscle necrosis, or seizures Dark-brown urine with microscopic hematuria
Guillain–Barré syndrome (acute idiopathic polyneuropathy)	Weakness begins in legs, spreads to arms, then face Difficulty breathing, swallowing, chewing Distal paresthesias Palpitations/tachycardia Facial flushing Sweating Loss of sphincter control Hyper- or hypotension
Lyme disease	Exposure to deer tick Neurologic deficits Rash (80% of patients—50% below the waist; 30% with target lesion) Polyarthritis
Postpoliomyelitis syndrome	New weakness Fatigue Pain Occurs decades after paralytic poliomyelitis
Myofascial pain syndrome	Similar presentation to FM Discrete muscular trigger points that, when stimulated, produce referred regional pain patterns Pain localized to shoulders, upper back, and neck
Hypernatremic myopathy	Dry skin Axillary and pubic hair loss Decreased libido Not thirsty Elevated serum sodium level Elevated creatine phosphokinase level Myogenic changes on electromyelogram
Rheumatoid arthritis	Morning stiffness Fatigue Focal tenderness Abnormal laboratory studies
Hypothyroidism	Muscle weakness Cold intolerance Goiter Dry skin and hair Weight gain Elevated level of thyroid-stimulating hormone
Depression or somatization syndrome	Fatigue No tender points Neurotic psychopathology
Chronic fatigue syndrome	Presents very similarly to fibromyalgia Viral titers may be elevated Tender points sometimes present
Viral infection	Usually acute onset Myalgias Usually resolves within 4 weeks

Source: Aminoff and Kerchner (2011); Brown (2013); Goroll and Mulley (2009); Marcus and Deodhur (2011).

FIBROMYALGIA

Anatomy, Physiology, and Pathology

Although there is no clearly identified pathophysiological process related to the development of FM (Firestone et al., 2012), some believe that the syndrome is partially the result of aberrant central pain mechanisms (Buckner Winfield, 2007; Goroll & Mulley, 2009) and dysfunction of skeletal muscle nociception (Gur & Oktayoglu, 2009). No specific structural abnormalities have been identified in FM (Winfield, 2007). There are, however, some biochemical markers associated with FM. These include increased levels of glutamate and substance P, both of which contribute to increased central nervous perception of pain (Firestone et al., 2012). Additionally, biochemical markers typically seen in depression (i.e., low levels of serotonin, norepinephrine, and dopamine) are seen in patients diagnosed with FM (Firestone et al., 2012).

Epidemiology

FM is seen mostly in women: 80% to 90% of those diagnosed with FM are women aged 30 to 50 years. The disease affects 3% to 9% of the U.S. population (Buckner Winfield, 2007; Firestone et al., 2012; Ziminski, 2008). FM symptoms vary in intensity, rarely occur in childhood, and affect “3 million to 6 million Americans, accounting for 2% of all primary care visits, 10% of internal medicine referrals, [and] up to 20% of rheumatology referrals” (Brown, 2013, p. 912).

Diagnostic Criteria

Traditionally, the 1990 American College of Rheumatology (ACR) criteria were used for the case definition of FM. For a variety of reasons, including the subjective nature of criteria and the lack of strict adoption by clinicians, new criteria were proposed in 2010 (Firestone et al., 2012; Wolfe et al., 2010, 2011). The 2010 ACR criteria are now being systematically adopted, with minor adaptations, in many countries (Fitzcharles et al., 2012, 2013). In many ways, the 2010 ACR criteria have revolutionized the approach to FM, including an increased emphasis on management of the disease in primary care.

Wolfe and Häuser (2011) note that the 1990 diagnostic criteria for FM rested completely on the physical examination of so-called tender points. By 2010 the ACR had revised the criteria to reflect the complaint of pain in various body regions, unrefreshing sleep and fatigue, somatic symptoms, and possible cognitive difficulties. An additional difference in the 2010 criteria is a nod to those who remain unconvinced of the existence of FM as a distinct syndrome: “A symptom severity scale that allows quantification of fibromyalgia-type symptom severity that can also be used in lieu of a fibromyalgia diagnosis for those uncomfortable with the fibromyalgia concept” (p. 2).

The ACR 2010 preliminary diagnostic criteria for FM state that the patient satisfies diagnostic criteria for FM if the following three conditions are met:

1. Widespread Pain Index ≥7 and Symptom Severity Score ≥5 or Widespread Pain Index between 3 and 6 and Symptom Severity Score ≥9.

2. Symptoms have been present at a similar level for at least 3 months.

3. The patient does not have a disorder that would otherwise explain the pain (Wolfe & Häuser, 2011).

A printable excerpt of the 2010 ACR guidelines that includes the Widespread Pain Index and Symptom Severity Score with instructions for administration and scoring is available at www.rheumatology.org/Practice/Clinical/Classification/Fibromyalgia/2010_Fibromyalgia_Diagnostic_Criteria_-_Excerpt/

In response to serious concerns about the existence of FM as a rheumatologic vs. neurologic vs. psychiatric disease vs. a somatic syndrome, Fitzcharles et al. (2013) compared international guidelines (from Canada, Germany, and Israel) with those of the U.S. ACR 2010 guidelines. There was “considerable consistency” (p. 7) among the guidelines. The conclusion was that FM is a distinct syndrome with overlaying rheumatologic symptoms among what may be many other symptoms. This said, FM is not exclusively a rheumatologic disorder. Their recommendation is that FM be diagnosed and treated in the primary care setting; they note that tender-point identification is not mandatory for establishing the clinical diagnosis (Fitzcharles et al., 2013).

History and Physical Examination

A comprehensive approach to the history is essential in the evaluation of FM because of the diffuse nature of the symptoms. A detailed review of systems should be conducted. Complaints of fatigue, numbness, stiffness, chronic widespread aching pain (usually without perceived weakness), headaches, and symptoms of irritable bowel syndrome predominate. A sleep history, with particular attention to the quality, not just the amount, of sleep, should be elicited (Buckner Winfield, 2007; Ziminski, 2008). Many patients with FM complain of waking from sleep unrefreshed. Symptoms of depression (feelings of sadness, change in sleeping or eating patterns, difficulty falling asleep, early morning awakening, difficulty completing normal daily activities, decreased libido, suicidal ideation, as well as weakness and fatigue) should be explored, as should those of hypothyroidism (cold intolerance, constipation, weight change, hoarseness, dry skin, menorrhagia, as well as weakness, fatigue, and depression). The impact of the symptoms on the patient’s relationships, employment, and social life and current stressors and coping methods should be assessed. Any history of fever, muscle injury, rash, or symptoms of arthritis must be elicited.

Ascertaining the location of the pain is no longer necessary in diagnosing FM. However, because the use of tender points for diagnosis is widespread in patient literature, patients may expect these to be examined. If for this, or any other reason, the provider wants to assess tender points, this is achieved by applying pressure to the tender points until the provider’s fingers blanch slightly. Symptoms of FM wax and wane and may be exacerbated by weather changes as well as poor sleep and other stressors.

The patient is usually afebrile and exhibits no weight loss. A complete physical examination should include in-depth musculoskeletal and neurologic examinations. The principal goal is to rule out causes for the symptoms other than FM. In the general examination, the skin, nails, mucous membranes, and fundi should be carefully evaluated for rheumatoid disease, myopathy, osteoarthropathy, thyroid disease, and focal pathology (Goroll & Mulley, 2009). The findings on the physical examination are typically normal, except for the usually symmetrical tenderness elicited by pressure on the tender points if included.

Indication of associated disease should be followed by diagnosis, as several diseases are often seen concomitantly with FM.

Diagnostic Studies

Laboratory studies are ordered to determine if the symptoms are from other diseases (as noted in the section “History and Physical Examination”). The results of laboratory studies are usually normal, but these studies are important to eliminate other serious conditions in the differential diagnosis. At the same time, without indication/high suspicion for other disorders, laboratory testing should be kept to a minimum. They should be used to confirm other-than-FM diagnoses; FM alone usually presents with normal lab tests (Fitzcharles et al., 2013).

Customary laboratory studies include a complete blood count (CBC) with differential and erythrocyte sedimentation rate (ESR). A thyroid-stimulating hormone (TSH) level is ordered to determine if the tiredness and weakness are a result of hypothyroidism. Additional laboratory tests may be ordered based on the patient’s history (e.g., Lyme titers can be useful if the patient has symptoms of Lyme disease; hepatitis panel if a patient’s lifestyle or travel indicates this is prudent). Further testing becomes costly and is usually noncontributory (Buckner Winfield, 2007; Firestone et al., 2012; Fitzcharles et al., 2013; Ziminski, 2008).

The diagnosis of FM is no longer considered one of exclusion. In most patients diagnosed with FM, more than one diagnosis is necessary to capture the whole spectrum of symptoms. Most importantly, other functional somatic syndromes (e.g., irritable bowel syndrome), mental disorders (e.g., depression or posttraumatic stress disorder [PTSD]), and somatic diseases (e.g., inactive or slightly active inflammatory rheumatic disease) can be diagnosed (Fitzcharles et al., 2013, p. 7).

Explore symptoms that are pertinent to the patient’s specific presentation, knowing that it is unlikely for an overall comprehensive diagnosis to be achieved at this time. Research in the field of FM is very active at this time; clinicians with a practice that includes FM should maintain currency with the findings.

Treatment Options, Expected Outcomes, and Comprehensive Management

Several evidence-based pharmacologic and nonpharmacologic treatment measures are available for the patient with FM. As always, the health care provider ensures that the patient is central to any plans for treatment. The patient–provider relationship becomes extremely important because FM is not easily diagnosed, nor is there “curative” treatment available to make the symptoms disappear. Patients must understand that FM is a disease that waxes and wanes, that no one therapy or treatment is recommended, and that different treatments may be tried before effective measures are found. Emphasize to the patient that an individualized treatment program will be developed that will probably include some treatments that do not work. Assure the patient that treatment(s) will be found. With the reassurance that you are partners in this search for relief, the patient will feel more secure with the ups and downs of treatment.

As is often the case when a specific etiology has not been determined, individualized, multimodal treatment measures are indicated. There have been international treatment guidelines from various professional groups since 2005. The primacy of pharmacologic intervention versus nonpharmacologic intervention has, however, been disputed. What is undisputed is that there are three major evidence-based recommendations: (a) stepped/graduated exercise programs and meditative movement therapies (e.g., yoga, tai chi); (b) cognitive behavioral therapy; and (c) pharmacologic agents directed at the patient’s specific constellation of symptoms (Ablin et al., 2013). Generally, narcotics are discouraged due to the high risk of complications (Gray, 2007). See Table 42.2 for generally accepted pharmacologic and nonpharmacologic treatments of FM. Patients typically see five clinicians over 8 years before a diagnosis of FM is established (Firestone et al., 2012). An atmosphere of support must be provided for patients diagnosed with FM. Often just the knowledge that they have a recognizable syndrome shared with others produces comfort (Fitzcharles et al., 2012). Patients must be assured that the intensity or duration of symptoms does not predict the long-term outcome and that FM is not a progressive disease. Any approach to treatment should be holistic and empathetic (Firestone et al., 2012; Goroll & Mulley, 2009); the goal of any therapeutic regimen is the resumption of normal or near-normal activity levels.

Pharmacologic treatment of FM is generally unsatisfactory. Nonsteroidal anti-inflammatory drugs (NSAIDs) and other pain relievers are generally not effective, but individual patients may report feeling better when taking those (Gray, 2007). See Table 42.2 for details of accepted treatment modalities. Specific medication dosage should be decided using manufacturer guidelines.

Most useful to patients with FM is a gradually progressive exercise regimen. The exact mechanism by which this helps is not clear, but many patients report feeling better when engaged in a regular exercise program. Stress reduction is an important aspect of the treatment of FM.

Teaching and Self-Care

Patients must be informed of the possibility that symptoms of FM may never completely resolve, but that increasing age and physical activity have been associated with decreased symptoms. Patients are often relieved when a primary care provider takes their complaints seriously and devotes the time and attention necessary to develop a plan with them. Patients and providers should plan together how patients can “take charge of their lives” and actively seek friends and social situations that may be stress reducing. Psychological support and counseling are also possible ways for patients to feel more secure in their ability to affect their health. The benefits of relaxation techniques and adequate nutrition should be underscored when working with patients battling FM.

Community Resources

Arthritis Foundation; www.arthritis.org/conditions-treatments/disease-center/fibromyalgia-fms/ Facts about FM; support and self-help groups by state; state and local chapters.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse, National Institutes of Health, 1 AMS Circle, Bethesda, MD 20892-0001; 301-495-4484; Toll Free: 877-22-NIAMS (877-226-4267); TTY: 301-565-2966; Fax: 301-718-6366; E-mail: NIAMSinfo@mail.nih.gov; www.niams.nih.gov