Guidelines for the diagnosis and management of fibromyalgia syndrome : Executive summary

1Division of Rheumatology, McGill University; 2Alan Edwards Pain Management Unit, McGill University Health Centre; 3Faculty of Law, Université de Montréal, Montreal, Quebec; 4Division of Rheumatology, Tufts University School of Medicine, Boston, Massachusetts, USA; 5Department of Family Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta; 6Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario; 7Centre de la recherche du Centre hospitalier de l’Université de Montréal, Department of Anesthesiology, Faculty of Medicine, Université de Montréal, Montreal, Quebec; 8Division of Physiatry, University of Toronto, Toronto; 9Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, London, Ontario; 10Patient representative Correspondence: Dr Mary-Ann Fitzcharles, Montreal General Hospital, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4. Telephone 514-934-1934 ext 44176, fax 514-934-8239, e-mail mary-ann.fitzcharles@muhc.mcgill.ca Although fibromyalgia (FM) has been recognized as a clinical syndrome for the past two decades, recent neurophysiological evidence of pain dysregulation has provided scientific validation. The controversy surrounding FM stems from the subjective nature of complaints and lack of any defining abnormal biological findings (1,2). This newer understanding has prompted clinical study and exploration of newer treatment options. In this spirit, the 2012 Canadian Guidelines for the diagnosis and management of FM syndrome were developed to provide directions for optimal patient care that align with the best available evidence (3). The clinical challenge remains because the cause of, the ideal treatment and any potential cures for FM are unknown. In addition, diagnosis is entirely dependent on patient report of symptoms and functional impairment, without any defining physical or laboratory abnormality. In addition to the pivotal symptom of chronic widespread pain, FM syndrome often includes fatigue, nonrestorative sleep, cognitive dysfunction and mood disorder, as well as variable somatic symptoms (4). Canadian prevalence rates are in the order of 2% to 3%, with females ori inal artiClE

reportedly affected more commonly than males, but with likely underdiagnosis in males (5). Although it occurs most frequently in middle-age women, FM can also affect children, teenagers and elderly patients.
Diagnosis may be delayed for years, with increased health care costs related to excessive investigation, frequent health care visits and referral to multiple specialists. With direct health care costs for Quebec patients with FM estimated to be more than CAD $4,000 per patient per year, an amount 30% higher than non-FM patients, an improved understanding of FM by the health care community may reduce patient suffering as well as the economic burden of this condition (6).
While there is currently no cure for FM, ideal management will address the combination of symptoms that may be present. Treatments must focus on active patient participation toward achieving healthrelated goals and incorporate nonpharmacological strategies as a foundation. Pharmacological treatment may also be required in a patient-tailored approach, with attention devoted to the risk-benefit ratio of any medication.
The Guidelines comprise 46 recommendations developed and arranged according to the subsections of diagnosis, management and follow-up (Appendix 1). Although there is copious literature available addressing various aspects of FM, the level of evidence available, other than for more recent drug studies, is mostly poor or lacking completely, with more than two-thirds of the recommendations graded as either level D or consensus. These guidelines are presented as recommendations pertinent to patient care in Canada, graded according to the level of supporting evidence, with the objective to facilitate clinical care. They should be viewed as an aid in the care of patients with FM, taking into consideration the unique needs of the individual, and should not be interpreted as the rules by which each patient should be managed.

Process of guideline development
The Guidelines were developed at the request of the Canadian Pain Society (CPS) to provide guidance for the diagnosis, management and patient trajectory of adults with FM in Canada, and the full document is available online through the CPS website (3). Because previous guidelines from the international community were based on available literature up to December 2006, updated guidance was needed in the light of recent progress in the understanding of FM (7)(8)(9).
Following a needs assessment with input from 139 Canadian health care professionals representing various disciplines, the Canadian Fibromyalgia Guideline Committee was assembled to oversee the guideline process. A literature search, directed by each question, was conducted at the McGill University Health Sciences library (Montreal Quebec). Databases searched were Embase, MEDLINE, PsycINFO, PubMed and the Cochrane Library, for results published during a 20-year period between 1990 and July 2010. A manual search of the references cited by original studies, reviews and evidence-based guidelines was also performed. Evidence was assigned according to the strength of the literature, and recommendations were drafted and graded according to the classification system of the Oxford Centre for Evidence-Based Medicine (Table 1) (10). Drafted recommendations were submitted via the Internet to 35 of the original 139 individuals who agreed to participate and constituted the National Fibromyalgia Guidelines Advisory Panel. Recommendations receiving 80% approval were accepted, while those not receiving approval were modified according to suggestions and resubmitted for voting. The document was reviewed by an external expert, as well as by the executive committees of the CPS and the Canadian Rheumatology Association, with resulting endorsement by both bodies. These guidelines will be in the governance of both endorsing bodies, who will oversee the updating process in 2015. All members of the Canadian Fibromyalgia Guideline Committee will participate in the dissemination process to enable maximum visibility across all relevant disciplines.
The needs assessment was supported by an unrestricted educational grant from Valeant (Montreal). The process of guideline development was facilitated by funding from the Louise and Alan Edwards Foundation. None of the funding sources had a role in the collection, analysis or interpretation of the data, or in the decision to publish the present report. Conflicts of interest for all members of the CFCG have been declared and are listed in the Guidelines document available online (3).

the diagnosis of FM reflects a paradigm shift
FM should now be positively diagnosed in the primary care setting following a comprehensive clinical evaluation and without need for unnecessary investigation. FM is recognized as a condition that fluctuates over time, and should no longer be viewed as an 'all or none' phenomenon, although factors influencing this variability in symptoms may not be easily identified. Chronic widespread pain, the pivotal and most important symptom, may have a burning quality suggestive of neuropathic pain, is not localized to any specific body tissue and tends to move from site to site. Symptoms of fatigue, sleep disturbance, cognitive changes, mood disturbance and various somatic symptoms may occur to a greater or lesser extent (4). Although many patients achieve some stability of this condition, symptoms seldom disappear completely (11).
A concept emphasized by these guidelines is that the diagnosis of FM should be made in the primary care setting and, in particular, does not require specialist confirmation. A second aspect that is highlighted is the fallacy associated with the tender point examination, a mainly subjective technique that is not supported by sound scientific basis and has been fraught with controversy. Therefore, contrary to previous beliefs, examination of tender points should not be used to either confirm or validate a diagnosis of FM (2). There is a strong call for the reduction of both excessive investigation and referrals to multiple specialists. Only simple laboratory tests should be performed, consistent with routine good health care, to ensure that some other, easily identifiable condition is not overlooked. The guidelines also acknowledge that criteria for the diagnosis of FM, developed by the American College of Rheumatology in 1990 and revised in 2010, were primarily intended for research purposes and should not be used to confirm a clinical diagnosis in an individual patient.
The clinical evaluation combined with simple blood tests will rule out most conditions that can present with body pain such as endocrine disease (hypothyroidism), rheumatic conditions (early inflammatory arthritis or polymyalgia rheumatica), neurological disease (myopathy or multiple sclerosis) or drug-induced conditions (lipid-lowering agents, aromatase inhibitors). Any additional testing should be specifically driven by the clinical findings, but with prudence.
Therefore, these guidelines recommend a paradigm shift whereby the responsibility for the diagnosis and management of FM is moved away from the specialist, with care concentrated in the primary care setting (12). Early diagnosis will avoid unnecessary investigations, a cause for patient uncertainty that prolongs health care behaviours and fosters medicalization (13)(14)(15). Attention can then be focused toward symptom management, attainment of optimal health, and maintenance or improvement of function. New symptoms in a patient with a previous diagnosis of FM should be evaluated according to good clinical standards, with the understanding that FM patients may eventually develop other illnesses unrelated to FM.
An elementary understanding of the neurophysiological concepts present in FM will reassure health care professionals of the validity of this condition and will also help guide rational treatment choices. Abnormalities in pain processing have been identified at various levels in the peripheral, central and sympathetic nervous systems, as well as the hypothalamo-pituitary-adrenal axis stress-response system, but these findings remain in the research domain and are not available for routine patient care (16)(17)(18).
The cause of FM is unknown. Familial studies have identified the possibility of genetic predisposition, with up to one-quarter of relatives of FM patients reporting chronic widespread pain (19,20). While no individual gene has been associated with FM, there is increasing evidence of a polygenic effect, with genes affecting serotoninergic, catecholaminergic and dopaminergic systems likely playing a role (21,22). Genetic factors may, therefore, predispose some individuals to a dysfunctional stress response via the hypothalamo-pituitary axis, and may be the setting whereby a triggering event may initiate clinical symptoms (23). Psychosocial distress, as well as early life adversity including abuse, have been shown to predict the onset of chronic, widespread pain (24,25). Primed by genetic factors, a physical or psychological trigger, as reported for nearly one-quarter to one-third of individuals, may lead to clinical expression of FM (26). Therefore, the expression of FM may be explained by a biopsychosocial model in which predisposition, triggering and other factors, such as depression, maladaptive coping or fearavoidance behaviour, contribute to chronicity.

the management of patients with FM
In the absence of a cure for FM, treatment recommendations should be directed at reduction of symptoms and fostering optimal function, with patient outcome goals clearly defined. Symptom-based management, taking into consideration the heterogeneous nature of this condition, can help to direct a patient-tailored, multimodal approach (27). Ideal management requires active patient participation in healthrelated practices and will centre on nonpharmacological strategies. Pharmacological treatments may be helpful for some patients, but with a need to evaluate efficacy and side effect profile (28). With average responses to therapy mainly modest at best, the essence of current evidence is that there is no 'gold standard' of treatment. Self-efficacy, attention to psychological distress and adherence to global treatment recommendations, strategies that may be augmented by cognitive behavioural therapy, will favourably influence outcome (29). Patients should be encouraged to be self-sufficient, develop good coping skills and pursue as normal a life pattern as possible.
Regular physical activity should form the cornerstone of treatment and received the highest grade of recommendation. To facilitate adherence, exercise of the patient's choice is encouraged and should be adjusted according to the individual patient's ability. This may take the form of an aerobic, strengthening, water, home-based or group program, depending on availability for an individual patient. Although many patients with FM are using various complementary and alternative medicines, in the absence of evidence, none can be recommended, but disclosure by the patient should be encouraged.
Symptom-based treatment represents a rational approach to pharmacological choices, with drugs impacting more than one symptom adding an advantage (16,27). There is a notion that the ideal treatment for FM is likely a combination of treatments, often in lower doses than reported in the study setting, with potential benefits of adherence. Although the traditional pharmacological treatment paradigm begins with the use of simple analgesics and tricyclic antidepressants, other agents that may be used include other antidepressants, gabapentinoids, dopaminergic agents and sleep modifiers. Once a drug treatment has been initiated, attention should be devoted to efficacy as well as the development of side effects, many of which can mimic symptoms of FM. Fatigue may be aggravated by gabapentinoids, antidepressants or analgesics; depression may be exacerbated by opioids and cannabinoids; gastrointestinal symptoms may be affected by nonsteroidal anti-inflammatory agents, opioids and antidepressants; and sleep disturbance may be aggravated by opioids and antidepressants.
Although care in a multidisciplinary setting may be desirable, this is not realistic, nor is it necessary for most patients (30). Access to a health care team member who is knowledgeable about FM can provide support, and may help the patient to develop coping strategies. Nursing support has been shown to reduce waiting time to consultation and increase patient satisfaction, but is still underused (31). Finally, public education and social marketing will help demystify FM and promote health.

Patient trajectory and outcome in FM
Ideal care of individuals with FM will be in the primary care setting; there is no clear advantage of care by a specialist (32)(33)(34)(35). Because the primary care physician has the best knowledge of the patient from the biopsychosocial perspective and is likely to have been managing the patient over time, the primary care setting must be the focal point of management. The need for education in this regard is imperative to provide confidence in management.
The health care community should discourage passive health-related practices and excessive dependence on health care professionals. Although clinic visits may be more frequent at treatment initiation, reduction of unnecessary health care contact when the patient is on a stable trajectory is mandatory. Clinical response may be reliably measured by a simple assessment of patient global status, rather than recourse to cumbersome questionnaires (36,37). Documenting patient goals and their levels of achievement is a strategy that has concrete meaning for a patient (38). Measurement of tender points is not a clinically relevant or reliable outcome measurement and should not be used to monitor patients (39).
Every effort should be made to maintain individuals with FM in the workforce. Their work ability is often contentious, with up to 35% receiving work disability benefits (40). Work modification that may include pacing may be an avenue to help retain individuals in the workforce. Although the physical and psychological demands of a job influence employment, the life situation, attitude and motivation, and ability to influence work parameters are additional contributing factors (41). Although return to work is perceived as an ideal health economic outcome, this may not be applicable for many women with FM who may be homemakers (42).
FM is a condition associated with considerable direct and indirect health care costs. A positive diagnosis may reduce costs by reducing tests, imaging, medication use, specialist referrals and primary care visits (14). In the United States, the cost for service utilization in an individual FM patient was more than US $2,000 in 1997, with reports in the order of CAD $4,000 per year per patient for Canada and Europe (6,(43)(44)(45). While nonpharmacological therapies have been demonstrated to be an effective and necessary component of treatment, they do, however, incur costs that are threefold greater than for pharmacological therapies. Comorbidities, such as depression, have also been shown to increase costs, warranting attention (44). Education and improved knowledge translation will enable health care professionals to diagnose and manage individuals with FM more effectively with associated cost containment.

Limitations
These recommendations should serve as a template for the care of adult FM patients, with the understanding that each patient is unique and treatments should be individualized. Evidence to support many aspects of these guidelines was either scanty or lacking, with reliance often placed on clinical experience and consensus of the participating health care professionals. Because access to care is not equal across all geographical regions of Canada, differences in care will be evident, with a need to harmonize treatments to the clinical setting. Although no cost analysis for the implementation of these guidelines has been performed, development of simple, clinically useful tools is in process. The full guideline document available on both the CPS and Canadian Rheumatology Association websites is extensive and should, therefore, serve as a reference, rather than a tool for day-to-day clinical practice.
We acknowledge that these guidelines propose fairly considerable changes in the way FM patients will be managed in the future. These suggestions may, at first, appear discomforting, but we believe that the medical community should be proactive in orchestrating the care of these patients. With a strong medical statement, policy makers and other stakeholders will be obliged to recognize this paradigm change.

CoNCLuSioN
FM is a valid syndrome affecting approximately one million Canadians. These guidelines address the complete spectrum of FM, are evidencebased, and were formulated by a large group of health care professionals representing various disciplines. They should provide direction for the rational treatment of FM, taking into consideration patient, provider and societal perspectives. It is hoped that the present report will help the health care community to confidently care for these patients with a positive approach that restores quality of life.

SuMMARy
The 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia were developed by a multidisciplinary team and are based on the available published evidence. Recommendations reflect this evidence combined with rational clinical judgment to facilitate the clinical care of patients. Fibromyalgia is a valid diagnosis that is a clinical construct without any defining physical abnormality or biological marker. Ideal treatment encompasses both nonpharmacological and pharmacological strategies, with emphasis on maintaining function. Several areas of paradigm change are addressed including a shift of diagnosis and treatment from the specialist setting to primary care. 2. All patients with a symptom suggesting a diagnosis of FM should undergo a physical examination, which should be within normal limits except for tenderness on pressure of soft tissues (ie, hyperalgesia [increased pain following a painful stimulus]) (level 4, grade D) (2,4,47).
3. Examination of soft tissues for generalized tenderness should be performed by manual palpation with the understanding that the specific tender point examination according to the 1990 American College of Rheumatology diagnostic criteria is not required to confirm a clinical diagnosis of FM (level 5, grade D) (1,2).

Testing and confirming the diagnosis
4. FM should be diagnosed as a clinical construct, without any confirmatory laboratory test, and with testing limited to simple blood testing including a full blood count and measurement of erythrocyte sedimentation rate and levels of C-reactive protein, creatine kinase and thyroid stimulating hormone. Any additional laboratory or radiographic testing should depend on the clinical evaluation in an individual patient that may suggest some other medical condition (level 5, grade D) (48,49). 5. The primary care physician should establish a diagnosis of FM as early as possible, without need for confirmation by a specialist, and communicate this diagnosis to the patient. Repeated investigations after diagnosis should be avoided unless driven by the onset of new symptoms or signs on physical examination (level 5, grade D) (13-15,34).
6. The American College of Rheumatology 2010 diagnostic criteria for FM can be used at initial assessment to validate a clinical diagnosis of FM, with the understanding that symptoms vary over time (level 3, grade B) (1,2,39).

differential diagnosis and coexisting conditions
7. Health care professionals should be aware that some medical or psychological conditions may present with body pain similar to FM, and patients with other medical illnesses may have an associated FM (level 5, grade D) (48,(50)(51)(52)(53) .

The health care team
8. Management of individuals with FM should be centred in the primary care setting with knowledgeable health care professionals and, ideally, where possible, this care may be augmented by access to a multidisciplinary team (level 1, grade A) (33,35) or team member to provide support and reassurance (level 3, grade C) (31,54).
9. Specialist consultation, including referral to a sleep specialist or psychologist, may be required for selected subjects, but continued care by a specialist is not recommended and should be reserved for patients who have failed management in primary care or who have more complex comorbidities (level 5, grade D) (34).

practice recommendations for FM: Section 2 Management
Treatment overview 13. A treatment strategy for patients with FM should incorporate principles of self-management using a multimodal approach (level 1 (27,28), grade A). It is recommended that attention should be devoted to individual symptoms in a patient-tailored approach, with close monitoring and regular follow-up, particularly in the early stages of management (level 5, grade D) (27).
14. Patients should be encouraged to identify specific goals regarding health status and quality of life at the initiation of treatment, with re-evaluation of goals during follow-up (level 5, grade D) (54).

nonpharmacological overview
15. Nonpharmacological strategies with active patient participation should be an integral component of the therapeutic plan for the management of FM (level 1 (28,59), grade A). Encouraging self-efficacy and social support will facilitate the practice of health promoting lifestyles (level 3 (60,61), grade D).
16. Individuals with FM should be encouraged to pursue as normal a life pattern as possible, using pacing and/or graded incremental activity to maintain or improve function (level 4, grade D) (62,63). 23. Patients should be encouraged to disclose use of complimentary and alternative medicines to the health care professional, who should be understanding and tolerant of this disclosure and should provide information on current evidence-based understanding of efficacy and risks where available (level 5, consensus).

pharmacological overview
24. Physicians should identify the most bothersome symptom(s) to help direct pharmacological treatments according to a symptom-based approach. An ideal pharmacological choice may address multiple symptoms simultaneously and may require a combination of medications, in which case attention must be paid to drug interactions (level 5 (16,27), grade D).
25. Pharmacological treatments should be initiated in low doses with gradual and cautious upward titration to reduce medication intolerance (level 5, grade D) (27) with regular evaluation regarding continued efficacy and side effect profile, with the knowledge that drug side effects may appear similar to symptoms of FM (level 5, consensus).
26. Physicians prescribing medications for FM should be open-minded and aware of the broader spectrum of agents available to treat symptoms, and should not confine treatments to a single category of medications (level 5, consensus).

Traditional pain-relieving therapies
27. Consistent with the WHO step-up analgesic ladder, acetaminophen may be useful in some patients, but with attention to safe dosing (level 5, consensus).
28. In the event that nonsteroidal anti-inflammatory drugs are prescribed, particularly for associated conditions such as osteoarthritis, they should be used in the lowest dose and for the shortest possible period of time, in view of potential serious adverse events (level 5, grade D) (78,79 11. Health care professionals should be knowledgeable that objective neurophysiological abnormalities have been identified in patients with FM in the research setting, but are not available in clinical practice for either the diagnosis or care of individuals with FM (level 5, grade D) (16,18).

12.
Patients and health care professionals should acknowledge that genetic factors as well as previous adverse events may have contributed to the development of FM, but focusing excessively on a triggering event could compromise patient care and should, therefore, be discouraged (level 5, grade D) (22,26,58).
practice recommendations for FM: Section 3 The outcome patient follow-up 36.
Clinical follow-up should be dependent on the judgement of the physician or health care team, with more frequent visits likely during the initial phase of management or until symptoms are stabilized (level 5, consensus).

37.
In the continued care of a patient with FM, the development of a new symptom requires clinical evaluation to ensure that symptoms are not due to some other medical illness (level 5, consensus).

38.
Patients should be informed that the outcome in many individuals is favourable even if symptoms of FM tend to increase and decrease over time (level 3, grade B) (92-94).

39.
Patients who have experienced previous adverse lifetime events that have impacted on psychological well-being and have not been effectively addressed should be offered appropriate support to facilitate attaining health-related outcome goals (level 5, consensus).

40.
Physicians should be alert that factors such as passivity, poor internal locus of control and prominent mood disorder may have a negative influence on outcome (level 5, consensus).

41.
Outcome can be measured by narrative report of symptom status or patient global impression of change, without need for more complex questionnaires (level 3, grade C) (36,37).

42.
Patient goals and their levels of achievement should be recorded as a useful strategy to follow outcome (level 5, consensus).

43.
Tender point examination should not be used as an outcome measure (level 3, grade C) (39).

44.
Physicians should encourage patients to remain in the workforce and, if necessary, may provide recommendations that could help maintain optimal productivity because outcome is generally more favourable for those who are employed (level 3, grade C) (95).

45.
Patients with FM on a prolonged sick leave should be encouraged to participate in an appropriate rehabilitation program with focus on improving function, including return to work if possible (level 5, grade D) (42).

46.
In persons with FM, other comorbid conditions including depression should be recognized and addressed to reduce health care costs (level 3, grade C) (96,97).