CLINICAL PRACTICE

Fibromyalgia: Diagnosing and managing a complex syndrome

Lauren Wierwille, MS, FNP-C, RN (Family Nurse Practitioner)
University of Maryland, Baltimore

Keywords Fibromyalgia; review; physical examination; pathophysiology; pharmacotherapy; complementary and alternative medicine (CAM); chronic illness. Correspondence Lauren Wierwille, MS, FNP-C, RN, 113 C Street, Suite G, Laurel, MD 20707. Tel: 301-617-2767; Fax: 301-617-3971; E-mail: lwier001@umaryland.edu Received: January 2010; accepted: September 2010 doi: 10.1111/j.1745-7599.2011.00671.x

Abstract
Purpose: The purpose of this clinical review is to clarify and discuss the diagnosis and management of bromyalgia. This includes typical signs and symptoms, pathophysiology, concomitant disease states, differential diagnoses, and recommended pharmacologic and nonpharmacologic treatment modalities. Data sources: The search included Evidence Based Medicine Reviews, Ovid MEDLINE, PubMed, and CINAHL. Search terms used: bromyalgia diagnosis, bromyalgia pathophysiology, incidence of bromyalgia, bromyalgia comorbidities, etiology of bromyalgia, bromyalgia treatment, American College of Rheumatology criteria. Search limited to sources from 1990 to 2010. Conclusions: Fibromyalgia is a complex muscular rheumatism that is not fully understood and often misdiagnosed. Signs and symptoms may overlap with many other conditions that must be properly ruled out to prevent diagnosis based upon arbitrary clinical judgment. Treatment is most benecial when tailored to individual patient presentation, and further research is warranted, particularly in the domains of pathophysiology and efcacy of treatment options. Implications for practice: An accurate knowledge of current research will aid the nurse practitioner in effectively prescribing evidence-based clinical interventions. Optimal bromyalgia management can be achieved through a multifaceted treatment approach and is enhanced with early identication of the disease process.

A 26-year-old female presents to the clinic with complaints of chronic, widespread muscle pain and tenderness that have been troubling her for over 3 months. Physical examination ndings reveal enhanced pain perception in response to mild sensory stimuli in greater than 10 specic locations dispersed throughout both sides of her upper and lower body. Additional symptoms include fatigue and morning muscle stiffness. The diagnosis is bromyalgia (FM). With complex and variable symptoms that can mimic several other medical conditions, FM is a common misdiagnosis (Cazzola et al., 2008; Goldenberg, Bradley, Arnold, Glass, & Clauw, 2008; Schneider, Brady, & Perle, 2006).

What is FM?
FM is a type of muscular rheumatism. Symptoms include a gradual onset of musculoskeletal pain often
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characterized as a deep and burning ache, variable in location, and radiating diffusely over many areas on the body. Associated symptoms include a triad of pain, sleep disturbance, and fatigue that exists in nearly all patients with FM. The temporal nature of these symptoms is variable, making it difcult to establish a universal pattern among patients. However, muscle stiffness and fatigue are reported to be most prominent in the early morning and in the early afternoon. Symptoms of FM have been reported to worsen with a range of factors that are largely cognitive, psychosocial, and behavioral in nature (Van Houdenhove & Luyten, 2008). Apart from pharmacologic and psychosocial therapies, alleviating factors common to a majority of FM patients have not been identied. Long-term studies regarding the course of FM after onset indicate that the signs and symptoms usually stabilize within the rst year of the syndrome and remain largely unchanged over time (Mease, 2005).

Journal of the American Academy of Nurse Practitioners 24 (2012) 184192 C 2011 The Author(s) Journal compilation C 2011 American Academy of Nurse Practitioners

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Prevalence
Prevalence studies estimate that 5 million adults in the United States have FM (Lawrence et al., 2008). Epidemiological and demographic evidence for the population at risk unwaveringly conclude females are diagnosed more often than males with a ratio of approximately 7:1, although studies have shown this statistic to be an overestimation (Weir et al., 2006). Incidence increases with age and is greatest in patients over age 50 (Lawrence et al., 2008). Specic trends in racial prevalence have yet to be determined because there is difculty in obtaining data. This is a result of FM being one among many diagnoses included in a group ICD-9 code of unspecied muscular inammation and pain (Centers for Disease Control and Prevention [CDC], 2009).

ogy of the syndrome is likely to play a signicant role in the diseases that frequently accompany FM (Goldenberg et al., 2008).

Pathophysiology of FM
Many sources have classied FM as idiopathic or poorly understood (Abeles, Pillinger, Solitar, & Abeles, 2007; Buskila & Sarzi-Puttini, 2008; Russell, 2006), but there are a handful of scientic theories that have been supported by evidence that when combined reveal much about the functional changes that occur in this abnormal disease state. Six probable pathological mechanisms behind the chronic, diffuse pain and other symptoms of FM are: (1) central nervous system (CNS) sensitization, (2) dysfunction of descending inhibitory pain pathways, (3) peripheral nervous system (PNS) sensitization, (4) release of inammatory mediators, (5) endocrine irregularity in the hypothalamic-pituitary-adrenal (HPA) axis, and (6) neurotransmitter abnormalities (Abeles et al., 2007; Krypel, 2009). Sensitivity of CNS neurons to painful stimuli is inherent for normal pain transmission. In FM, the CNS neurons become hypersensitive, which exaggerates and prolongs pain sensation from an acute protective mechanism to one that is chronic and pathologic. Concurrently, the negative feedback loop that physiologically initiates the cessation of pain sensation is inhibited, causing the already amplied pain sensation to continue indenitely. The PNS neurons are similarly affected, causing enhanced pain perception that can manifest as incessant cutaneous allodynia in extreme cases. When mild tactile stimulation is transmitted as pain from the periphery to the brain, regions in the cortex send CNS signals, which in turn result in the perception of musculoskeletal pain. These peripheral pain signals also reach the limbic structures of the brain and are thought to be responsible for concomitant psychiatric conditions (Nielsen & Henriksson, 2007). The mechanism behind PNS sensitization forms a cycle. When peripheral sensations reach the limbic system, transmissions through the HPA axis subsequently activate the sympathetic nervous system (SNS). Because of CNS hypersensitivity, the HPA axis is continually stimulated to initiate a chronic SNS stress response from the increased pain perception. It is this sustained SNS activation that eventually leads to PNS hypersensitivity. This PNS hypersensitivity begins the cycle again by maintaining the abnormal peripheral sensations that cause the stress response. Additionally, the chronic SNS stress response causes muscles throughout the body to contract, leading to muscle hypoxia that manifests as fatigue. When the muscles do not receive enough oxygen, glial cells release
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Etiology
The etiology of FM is multifactorial. However, several risk factors have been identied that may predispose a person to FM. These include a familial or genetic component, traumatic experiences that occur especially in the early years of life, personality type, lifestyle choices, and previous episodes of depression (Van Houdenhove & Luyten, 2008). Precipitating factors are highly individualized, and the majority of factors are divisible into two categories: physical stressors and psychosocial stressors. The hypothesis that vaccinations contribute to the development of FM has not been supported by research (Buskila, Atzeni, & Sarzi-Puttini, 2008).

Concomitant disease states

When considering the clinical picture of a patient diagnosed with FM, it is important to be aware of several concomitant disease states that are associated with the diagnosis. The syndrome and its associated comorbidities cover many clinical domains, including musculoskeletal, rheumatological, neurological, psychological, and gastrointestinal (Goldenberg et al., 2008). The following comorbidities are anywhere from two to seven times more likely to be present in FM patients than those without the syndrome (Weir et al., 2006):

r r r r r

rheumatic conditions (e.g., rheumatoid arthritis and systemic lupus erythematosus), chronic fatigue syndrome, irritable bowel syndrome, headache, psychiatric conditions such as anxiety and depression.

The relationship of FM with such conditions is uncertain, but the evidence for familial, genetic, and environmental factors involved in the multifaceted pathophysiol-

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many inammatory mediators that also contribute to the pathophysiology of FM in an unknown way (Krypel, 2009). Sleep disruptions associated with FM are a direct manifestation of endocrine dysfunctions in the HPA axis. During times of chronic stress, the body experiences continual increases in cortisol secretion. Over time, the body attempts to restore homeostasis and overcompensates for the cortisol elevation by intensifying the normal physiological negative feedback loop initiated by glucocorticoids, resulting in a cortisol deciency. Rather than having the continuous increased levels of cortisol that naturally exist during stress and during the early phases of FM, cortisol secretion becomes diminished later into the course of the syndrome, resulting in disrupted sleep (Abeles et al., 2007). The use of prescription glucocorticoids perpetuates the symptoms of FM in most patients as a result of further intensication of the normal physiological negative feedback loop (Russell, 2006). When the body is in a state of hypocortisolemia as seen with FM, it becomes increasingly sensitive to this negative feedback loop, but the precise mechanisms responsible for the perpetuation of FM symptoms has not been denitively claried (Macedo et al., 2008; Tanriverdi, Karaca, Unluhizarci, & Kelestimur, 2007). As for the neurotransmitters, abnormalities of both dopamine and serotonin are involved in FM. Plasma and cerebrospinal uid serotonin have been found to be lower in patients with FM when compared with patients that do not exhibit this pain syndrome. Serotonin is partly responsible for the inhibition of pain pathways and therefore the lack of this neurotransmitter in FM patients adds to the problem of stopping the pain response. Dopamine levels in FM patients are also decreased when compared with patients that do not exhibit a pain syndrome. In times of acute stress, an increase in dopamine levels is the natural physiologic response for enhanced analgesic effects; however, in times of continual stress, dopamine will become decreased as the body overcompensates in an attempt to restore homeostasis (similar to cortisol). This dopamine deciency then contributes to the increased pain perception. The result of this dopamine deciency in FM patients also creates an additional risk factor for depression (Krypel, 2009).

tle upon this diagnosis following negative testing for other differentials (Sim & Madden, 2008). Given this, the American College of Rheumatology (ACR) established two points of reference for the diagnosis of FM in response to a study of 558 FM patients: (1) musculoskeletal pain that is present for at least 3 months and located diffusely in all four body regions (divided horizontally at the waistline and vertically at the midline) as well as in the axial skeleton and (2) pain that is elicited on palpation of at least 11 of 18 specied tender points that have been designated by ACR for FM musculoskeletal assessment (Cazzola et al., 2008). This framework for diagnosis has received criticism because it only accounts for the pain aspects of the syndrome. An estimated 80% of patients with FM actually exhibit a lesser number of tender points than the ACR criteria requires (Mease, 2005). See Figure 1 for a diagram of these tender points. Interestingly, the pathophysiologic mechanisms of FM have been correlated with the ndings of skin biopsies from FM patients. Under the premise that the PNS abnormalities associated with FM should be detectable in the periphery, several studies have been conducted that analyzed skin biopsies from ACR tender point locations in patients with FM. The results consistently showed visible demyelination of neurons and inammation of peripheral nerve bers on histological examination that are speculated to result from HPA axis dysfunction and the effects of chronic stress. These studies have advanced FM research by providing additional clues to pathophysiologic mechanisms for future examination. Further research is still necessary to determine if skin biopsy may become a useful diagnostic aid (Kim, 2007).

Differential diagnoses
When a patient exhibits the typical signs and symptoms of FM, there are several other diagnoses to consider that have similar characteristics or overlapping clinical features. The ACR guidelines for FM diagnosis require chronic, widespread, musculoskeletal pain that can be elicited on palpation of tender points, features that are present in several other disease processes in addition to FM. This fact caused one of the initial creators of the ACR criteria to publish an editorial encouraging healthcare providers to stop using it denitively for FM diagnosis in the clinic (Wolfe, 2003). In 2007, Harth and Nielson published a review of the controversy between whether or not these tender points are worthwhile for clinical evaluation and concluded that despite the difculties associated with the ACR criteria, it is a more benecial and objective diagnostic aid than other suggested assessment methods for FM pain.

Diagnosis of FM
Many cases of FM do not precisely align with a standardized set of diagnostic criteria. However, it is not believed to be a diagnosis of exclusion, although some healthcare providers have labeled it as such. Because there is an absence of absolute, denitive diagnostic criteria with universal applicability, providers often set186

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B E D

F G H I

A) Occiput: bilateral, at the suboccipital muscle insertions. B) Low cervical: bilateral, at the anterior aspects of the intertransverse spaces at C5-C7. C) Trapezius: bilateral, at the midpoint of the upper border. D) Supraspinatus: bilateral, at origins, above the scapula spine near the medial border. E) Second rib: bilateral, at the second costochondral junction, just lateral to the junctions on upper surfaces. F) Lateral epicondyle: bilateral, 2 cm distal to the epicondyles. G) Gluteal: bilateral, in upper outer quadrants of buttocks in anterior fold of muscle. H) Greater trochanter: bilateral, posterior to the trochanteric prominence. I) Knee: bilateral, at the medial fat pad proximal to the joint line.

Figure 1 FM tender points. Note. From Cazzola et al. (2008), with permission.

Rather than assuming a diagnosis of FM, carefully considering a multitude of potential diagnoses will decrease the likelihood of a misdiagnosis. Five of the most common differentials that the nurse practitioner (NP) can consider in patients exhibiting symptoms of FM are mental health disorders, hypothyroidism, rheumatoid arthritis, adrenal dysfunction, and multiple myeloma

(Schneider et al., 2006). These are all conditions that have been misdiagnosed as FM and will be discussed in detail. See Table 1 for a thorough list of differential diagnoses associated with FM as well as appropriate diagnostic testing if available for the conrmation or exclusion of each. If the diagnostic test results are positive for any of the differentials listed in the table, a diagnosis of FM is likely inappropriate for that patient. Psychiatric diagnoses are often an underlying reason for symptoms similar to those of FM. While a patient may have a mental health disorder concomitantly with FM, it can also be the actual cause of FM-like symptoms. Posttraumatic stress disorder (PTSD), anxiety disorders, and depression are the most common mental health problems in which patients may exhibit such symptoms, but there is not an established pattern of which patients with mental health disorders will exhibit symptoms and which will not. However, those who do exhibit symptoms have been studied with positron emission tomography scans. These scans show activation of limbic structures in the brain when what would ordinarily be nonpainful stimuli to an unaffected individual is received. It is also important to be aware that these mental health disorders may present as signicant sleep disorders or chronic fatigue syndrome. If a patient exhibiting FM-like symptoms is found to have a newly diagnosed mental health disorder, treating the mental health disorder might alleviate the problem altogether (Schneider et al., 2006). Symptoms of hypothyroidism that are similar to FM include fatigue, disrupted sleep of poor quality, and generalized muscular pain. The symptoms differ from FM in that hypothyroidism does not typically manifest with the severity of pain or the hypersensitivity to tactile stimulus that is seen in FM. Also, hypothyroidism does not present with the same collection of concomitant disease states that are important clues to the diagnosis of FM. Laboratory thyroid stimulating hormone (TSH) can be drawn for any patient reporting fatigue with musculoskeletal pain to rule out a thyroid abnormality. A thorough familial and personal history of the patient will also aid in bringing the many facets of FM together into one clinical picture (Schneider et al., 2006). Rheumatoid arthritis and other inammatory rheumatic diseases show signs and symptoms similar to FM. Specically, patients with rheumatic diseases can report widespread musculoskeletal pain that might have similar timing (worse in morning and/or early afternoon) and be accompanied by muscular stiffness. However, FM does not include joint inammation, localized edema and deformity, or a vascular rash that can be characteristic of inammatory rheumatic diseases. A rheumatic panel that includes rheumatoid factor and erythrocyte sedimentation rate (ESR) or C-reactive
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Table 1 Differential diagnoses for FM and corresponding diagnostic testing options Differential diagnoses Adrenal dysfunction Anemia Bone marrow disease Chronic fatigue syndrome Functional disorders (e.g., intestinal dysbiosis, subtle endocrine imbalances, postviral immune suppression) Hypothyroidism Lyme disease Psychiatric conditions (e.g., anxiety, depression, PTSD) Multiple sclerosis Phenomenological Referred Myofascial Pain Rheumatoid autoimmune disorders (e.g., rheumatoid arthritis, ankylosing spondylitis, scleroderma) Sleep disorders Spinal facet pain or sacroiliac joint pain Spinal disc herniation Systemic inammation or infection Vitamin and/or mineral deciency Diagnostic testing options Morning serum cortisol, urinary catecholamine metabolites CBC with differential, RBC indices (MCV, MHC, MCHC) WBC differential, ESR, CRP, CMP Clinical history Standard laboratory testing yields unclear results Thyroid function tests (T3, T4, TSH) Lyme titer, CMP Refer to DSM-IV MRI scan, lumbar puncture, evoked potential testing Muscular tender points on physical examination Rheumatic prole (rheumatoid factor, ESR/CRP), ANA EEG sleep studies Radiologic studies (MRI scan, CT scan), bone scans (minimal diagnostic assistance) MRI scan WBC differential, ESR, CRP, CMP B vitamins, magnesium, malic acid, complete nutrition assessment

ANA, antinuclear antibody; CBC, complete blood count; CMP, complete metabolic prole; CRP, C-reactive protein; CT, computerized tomography; DSMIV, diagnostic and statistical manual of mental disorders; EEG, electroencephalogram; ESR, erythrocyte sedimentation rate; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; MRI, magnetic resonance imaging; PTSD, posttraumatic stress disorder; RBC, red blood cell; T3, triiodothyronine; T4, thyroxine; TSH, thyroid stimulating hormone; WBC, white blood cell. Note. Adapted from Schneider et al. (2006).

protein (CRP) is an important laboratory test to include when patients present with musculoskeletal/joint pain because abnormally elevated levels on serologic testing can alert the provider to a potential inammatory rheumatic abnormality other than FM (Holman, 2009). The results of an antinuclear antibody (ANA) test can help differentiate FM from rheumatoid arthritis (positive in approximately 40% of cases); a negative ANA does not rule out the presence of rheumatoid arthritis, but a positive ANA can help rule the condition in. Joint x-rays may also be benecial in the differential diagnosis, and referral to a rheumatologist can be helpful if the diagnosis is unclear (Majithia & Geraci, 2007). A diagnosis of FM should not be given unless symptomatology and physical examination are in accordance with the ACR criteria and all other diagnostic tests are negative for an underlying, organic cause (Schneider et al., 2006). Adrenal dysfunction is another condition that might present with symptoms similar to FM, especially if the patient is chronically fatigued. In order to differentiate between FM and an adrenal dysfunction, evaluation of adrenal status can be accomplished by obtaining a morning serum cortisol level (that may be lower than normal) and urinary catecholamine metabolites (that may be greater than normal). These ndings may also be consis188

tent with PTSD, so it is imperative to do a thorough history and identify the likely need for psychological counseling in addition to direct treatment of the immediate cause of adrenal dysfunction (Schneider et al., 2006). Although it is a relatively rare diagnosis, multiple myeloma is a differential that must always be ruled out when a patient presents to the clinic with widespread muscular pain similar to FM, particularly if the onset occurs when the patient is greater than 60 years of age. Both have similar manifestations of chronic pain that is gradual in onset, but multiple myeloma is more likely to occur at an advanced age, whereas FM occurs in adults of all ages. The most essential history elements to obtain include a family history or personal history of cancer in any location because of the potential for metastases (Holman, 2009).

Treatment of FM
In the absence of one specic treatment algorithm that is universally accepted for FM, there are various treatment modalities currently being used and studied. While pharmacologic therapies are most preferred by patients because of their simplicity and minimal interference with daily life, there is conicting evidence to show the

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efcacy of such drug treatments. There are also several nonpharmacologic therapies that are less preferred by patients but have been shown to signicantly improve FM symptoms in both short and long-term studies (Abeles, Solitar, Pillinger, & Abeles, 2008). Two guidelines for pharmacologic recommendations based upon FM drug therapy studies are those published in 2007 by the European League Against Rheumatism (EULAR) and those published in 2005 by the American Pain Society (APS). Both guidelines rank individual pharmacologic agents as either having strong, moderate, or weak efcacy based upon the type of evidence included in the reviews. Strong efcacy indicates that metaanalysis and systematic reviews of randomized controlled trials show signicant efcacy for the drug therapies in reducing FM pain; moderate efcacy indicates that the evidence came from cohort studies, case control studies, and cross-sectional studies; and weak efcacy indicates evidence from case reports and healthcare provider experience (Krypel, 2009).

Rooks, 2007). Herbals and supplements, however, have not been studied thoroughly enough to yield results signicant for any benet in FM treatment (Krypel, 2009). See Table 2 for detailed information regarding pharmacologic treatment modalities for FM.

Nonpharmacologic modalities
Complementary and alternative medicine therapies, particularly acupuncture, have also been used as a potential treatment for FM if the patient elects this option. The recommendations for acupuncture therapy are inconsistent, and the majority of studies conclude that there is not enough evidence in support of its efcacy (Abeles et al., 2008; Mayhew & Ernst, 2007). Likewise, a systematic review of exercise therapy for improving FM symptoms resulted in mixed evidence. This review concluded that there are benets to aerobic exercise in reducing symptoms of FM, but the results were not statistically signicant (Busch, Schachter, Overend, Peloso, & Barber, 2008). Lastly, because psychiatric concomitant diagnoses are common with FM and can play a major role in worsening the psychological perception of pain, psychosocial therapies such as cognitive behavioral therapy and biofeedback have a moderate to strong effect in reducing the severity of symptoms (Mease, 2005). See Table 3 for a list of nonpharmacologic treatment modalities recommended by the APS and/or EULAR for FM.

Pharmacologic modalities
The major drug classes considered for treatment of FM include antidepressants, muscle relaxants, CNS agents, dopamine agonists, and analgesics. Antidepressants demonstrate the ability to improve a majority of FM symptoms, including pain and depression, and they are particularly useful in treating the sleep disturbances and fatigue associated with FM by increasing deep sleep. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have moderate to strong efcacy in reducing FM pain according to both the EULAR and APS guidelines. They are recommended over the tricyclic antidepressants (TCAs), which also have moderate to strong efcacy, because SSRIs and SNRIs have milder side effects. One particular SNRI, amitryptyline, is ranked as strong efcacy by EULAR and APS (Hauser, Bernardy, & Uceyler, 2009; Krypel, 2009). Overall, muscle relaxants demonstrate weak efcacy. The single exception to this is cyclobenzaprine, which is considered strongly effective by APS and is unrated by EULAR (Krypel, 2009). In a double-blind controlled study, the CNS agents pregabalin and gabapentin were both statistically signicant in reducing pain associated with FM when compared with placebo (Abeles et al., 2008). The dopamine agonist pramipexole has strong efcacy according to EULAR for decreasing FM pain, but is unrated by APS. As for analgesics, tramadol alone or a combination pill of tramadol and acetaminophen are the recommended choices from this drug class, exhibiting moderate efcacy for reducing FM pain (Krypel, 2009;

Customized treatment
There are many interventions to choose from when creating a treatment plan for this pathologically complex syndrome. FM is currently treated empirically on a case-by-case basis; there is not one standardized treatment plan that is effective in all FM patients. Because the symptomatology of FM varies substantially from person to person, it is necessary to tailor the intervention(s) used to the signs and symptoms that each patient exhibits (Abeles et al., 2008). Research indicates that customized treatment plans designed by either the NP or a rheumatologist that account for the needs of patients, their preferences, and the concomitant disease states are the best known treatment strategies for FM (Van Houdenhove & Luyten, 2008). Further research is warranted to conrm that this treatment strategy signicantly and consistently yields the most optimal patient outcomes. Because FM is a condition diagnosed and managed in primary care, a referral to a specialist is most often warranted for assistance in managing more refractory cases. Guidelines for referring FM patients are not clearly established because the appropriate specialist is best determined by individual presentation, which is extremely
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Table 2 Pharmacologic treatment modalities for FM Drug (class) Amitriptyline (TCA) Dosage 10 mg qhs; 2550 mg qhs Pharmacodynamics Increases 5-HT and NE at CNS synapses by decreasing reuptake. Increases 5-HT at CNS synapses by inhibiting reuptake. Increases NE and 5-HT at CNS synapses by inhibiting reuptake. Increases 5-HT and NE at CNS synapses by inhibiting reuptake. Mildly inhibits CNS DA reuptake. Reduces contractile activity of and motor neurons. Inhibits excitatory NT release by binding to 2- subunit of voltage-gated calcium channels in CNS. Inhibits excitatory NT release by binding to 2- subunit of voltage-gated calcium channels in CNS. Acts as an agonist to DA2 and DA3 receptors, thereby increasing DA effect. Blocks CNS ascending pain pathways by weakly binding to -opiate receptors. Mildly inhibits 5-HT and NE reuptake. Contraindications Acute period after MI; pregnancy (C); lactation; history of seizures; children <12 years. Hypersensitivity to SSRIs; with MAOIs or thioridazine; pregnancy (C); children <7 for OCD or <8 for depression. Uncontrolled narrow-angle glaucoma; with MAOIs; pregnancy (C); lactation. Uncontrolled narrow-angle glaucoma; with MAOIs; pregnancy (C); lactation. Acute period after MI; cardiac arrhythmias; heart block; conduction disturbances; CHF; hyperthyroidism; pregnancy (C); lactation. Hypersensitivity to pregabalin or gabapentin; alcohol; pregnancy (C); lactation. Hypersensitivity to gabapentin; pregnancy (C); lactation. Hypersensitivity to pramipexole or ropinirole; pregnancy (C); lactation. Hypersensitivity to opioids; with MAOIs; intoxication with alcohol; substance abuse; with obstetric pre-operative medication; pregnancy (C); lactation; children <16 years.

Fluoxetine (SSRI)

20 mg qd; 2080 mg qd

Milnacipran (NSRI) Duloxetine (SNRI)

25 mg qd; 100 mg bid 30 mg qd; 60 mg qd bid

Cyclobenzaprine (muscle relaxant) Pregabalin (CNS agent)

10 mg qhs; 10 mg qhs20 mg bid 50 mg tid; 100150 mg tid

Gabapentin (CNS agent) Pramipexole (dopamine agonist) Tramadol (opiate analgesic)

300 mg qhs; 300600 mg tid

0.125 mg tid; 0.51.5 mg tid 50 mg qd; 50100 mg tid

5-HT, serotonin; bid, twice daily; CHF, congestive heart failure; CNS, central nervous system; DA, dopamine; MAOI, monoamine oxidase inhibitor; MI, myocardial infarction; OCD, obsessive-compulsive disorder; NE, norepinephrine; NSRI, norepinephrine serotonin reuptake inhibitor; NT, neurotransmitter; qd, once daily; qhs, at bedtime; SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; tid, three times daily. Note. Adapted from Abeles et al. (2008), Krypel (2009).

Table 3 Nonpharmacologic treatment modalities for FM Acupuncture Biofeedback Chiropractic manipulation Cognitive behavioral therapy Heated pool therapy Physical therapy Psychological support Relaxation techniques Tailored exercise programs Therapeutic massage Note. Adapted from Krypel (2009).

tologists, pain specialists, psychologists, psychotherapists, and others depending upon the individual presentation and need.

Assessment of patient outcomes

When a customized treatment plan is implemented, follow-up visits should occur periodically for continued assessment of the syndrome course. Length between visits is variable and dependent upon the therapies chosen and the severity of the symptoms. The main goal of therapy is to minimize debilitation and improve quality of life for patients with FM by alleviating the burden associated with the pain and accompanying disease states. Objective and measurable goals for treatment outcomes can be set with each FM patient based upon the clinical domains of the individual presentation. The recommendation and utilization of available community resources is just one way for the NP to assist the patient in meeting these goals.

variable. When the psychological aspects of the disorder are a more prominent problem, a psychotherapist may be a tting referral. Or if neurological pain symptoms are the most debilitating for the patient, a pain center or neurologist may be the best referral. Specialists to be considered for the management of FM include neurologists, rheuma190

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The Outcome Measures in Rheumatology Clinical Trials (OMERACT) conclude that a measurement system is necessary to aid in monitoring the progression of FM symptoms and evaluating the effectiveness of a given treatment plan for follow-up visits. Conclusions from OMERACT indicate that the most important criterion for measuring FM outcomes is collection of baseline data at the initial diagnosis (Mease, 2005). Subsequent visits that utilize the same measuring instrument and technique to monitor disease progression and symptom improvements allow greater accuracy in evaluating the effectiveness of interventions. Expected outcomes of treatment are a decrease in pain perception as subjectively rated by the patient as well as improvements in other related conditions being treated (e.g., depression score decreased when measured by an inventory questionnaire, etc.; Mease, 2005).

a customized plan is the most supported treatment approach recommended to date.

Acknowledgments
I would like to thank Christina Calamaro, PhD, for her assistance in mentorship and manuscript editing; the current faculty of the University of Maryland, Baltimore family nurse practitioner program for their teaching expertise; and Darryl Roberts, PhD, for his assistance with review and comments on the initial draft.

References
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Prognosis of FM
FM typically stabilizes within the rst year of the syndrome course and does not usually worsen significantly over time, so the incidence of debilitation is nominal (Mease, 2005). There is no cure for FM, so it is not a condition that has recurrences (Goldenberg et al., 2008). Mortality risk associated with FM is estimated to be 30% greater than patients without the syndrome (Macfarlane, 2005). This risk is not attributable to the disease process itself but to the sedentary lifestyle that a majority of FM patients adopt when their pain intensity increases to the point of compromising their ability to comfortably tolerate activity (Macfarlane, 2005). Living with burdensome FM symptoms can have a negative effect on quality of life and can especially hinder elderly patients from carrying out activities of daily living (Goldenberg et al., 2008). The focus of current research is on maximizing treatment options and combinations to optimize patient functioning. During this transitional phase of reexamining old therapies and discovering new, denitive, evidence-based statements cannot be made about patient functioning after FM treatment.

Conclusion
The review of current research regarding the diagnosis and management of FM offers a framework to guide the NP in making clinical decisions based on evidence. FM is a pathologically complex syndrome necessitating a thorough assessment of patients presenting with widespread, musculoskeletal pain, or any other symptoms consistent with this diagnosis. Purposeful selection and utilization of pharmacologic and/or nonpharmacologic modalities in

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Fibromyalgia

L. Wierwille

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widespread pain. Journal of Manipulative and Physiological Therapeutics, 29(6), 493501. Sim, J., & Madden, S. (2008). Illness experience in bromyalgia syndrome: A metasynthesis of qualitative studies. Social Science & Medicine, 67(1), 5767. Tanriverdi, F., Karaca, Z., Unluhizarci, K., & Kelestimur, F. (2007). The hypothalamo-pituitary-adrenal axis in chronic fatigue symdrome and bromyalgia syndrome. Stress, 10(1), 1325. Van Houdenhove, B., & Luyten, P. (2008). Customizing treatment of chronic fatigue syndrome and bromyalgia: The role of perpetuating factors. Psychosomatics, 49(6), 470477. Weir, P. T., Harlan, G. A., Nkoy, F. L., Jones, S. S., Hegmann, K. T., Gren, L. H., & Lion, J. L. (2006). The incidence of bromyalgia and its associated comorbidities. Journal of Clinical Rheumatology, 12(3), 124128. Wolfe, F. (2003). Stop using the American College of Rheumatology criteria in the clinic. Journal of Rheumatology, 30(8), 16711678.

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