Diagnosis

2012 Canadian Guidelines for the Diagnosis and Management of Fibromyalgia Syndrome

Mary-Ann Fitzcharles1,2, Peter A. Ste-Marie2,3, Don L. Goldenberg4, John X. Pereira5, Susan Abbey6, Manon Choinière7, Gordon Ko8, Dwight Moulin9, Pantelis Panopalis1, Johanne Proulx10, Yoram Shir2

1.1 How is fibromyalgia diagnosed?

FM is a syndrome of diffuse body pain with associations of fatigue, sleep disturbance, cognitive changes, mood disturbance, and other variable somatic symptoms [3]. A diagnosis of FM is made following a clinical evaluation which includes a history of current complaints, attention to past health status and a physical examination, without any confirmatory diagnostic test. Although criteria for the diagnosis of FM were developed for research purposes, they may be used to validate a clinical diagnosis.

1.1.1 The clinical presentation of fibromyalgia

FM may affect persons of all ages and of both genders, but is most prevalent in female patients in the third to fifth decade. There are no studies examining diagnostic criteria in the clinical setting and there is no confirmatory laboratory test for FM [11]. Symptoms wax and wane over time, but seldom disappear [12, 13].

1.1.2 The symptom complex in persons with fibromyalgia

  • a) Pain

  • Pain is the primary complaint in persons with FM and should have been present for at least 3 months. Pain onset is usually insidious, sometimes beginning in a localized area, may initially be intermittent, and then progressively becomes more persistent. Although pain is felt in muscle or joint areas, there is no physical abnormality of these tissues. A neuropathic mechanism to the pain may be suggested by report of a burning quality to the pain [14, 15]. Pain may vary in location and intensity from day to day, and can be modulated by factors such as weather or stress [16]. Cold and humid weather tends to be
    associated with increased symptoms [16, 17]. Although the most frequently reported sensory symptom in FM is pressure induced pain, this was only reported to be severe in 58% of FM patients [14].

  • b) Other associated symptoms present in FM

  • Symptoms other than pain are common in FM and can contribute to one third of the global suffering [2, 3, 18].

    1. Fatigue
    2. Fatigue, reported to be present in over 90% of FM patients, is the most common associated complaint [3]. Fatigue may even be more disabling than pain for some, and contributes to subjective report of functional impairment. Fatigue is challenging to measure, with reliance on subjective patient report to gauge severity. Overlap with chronic fatigue syndrome has been described, although pain is more prominent in patients with FM [19].

    3. Nonrestorative sleep
    4. Nonrestorative sleep is associated with FM [20]. Abnormal components of sleep that have been measured include sleep latency, sleep disturbance, and fragmented sleep leading to impaired daytime function [21, 22]. Poor sleep negatively impacts fatigue, affect, and pain, with improvement in these parameters when sleep specifically is addressed [23-26]. Other sleep disorders such as restless leg syndrome or sleep apnoea may also occur in patients with FM.

    5. Cognitive dysfunction
    6. Cognitive dysfunction which includes poor working memory, spatial memory alterations, free recall, and verbal fluency associates with pain in FM as well as other pain patients and is different from healthy controls [27-30].

    7. Mood disorder
    8. Mood disorder, including depression and/or anxiety, is present in up to three quarters of persons with FM, but mood disorders and FM are likely distinct [31]. Anxiety commonly coexists with depression, but is also independently increased in FM patients [32, 33]. Depression is influenced by low family cohesion, high pain and helplessness, and passive coping skills [34]. First-degree relatives of individuals with either FM or major depressive disorder (MDD) demonstrated similar rates of MDD suggesting that these two conditions share similar risk factors which may be genetically driven [35].

    9. Pain-related somatic symptoms
    10. Somatic symptoms, including irritable bowel syndrome, migraine headaches, severe menstrual pain, lower urinary tract symptoms, myofascial facial pain, and temporomandibular pain have all been associated with FM [36-39].

    11. Non-pain related symptoms
    12. Sexual dysfunction has recently been reported to occur in 97% of FM patients [40]. FM patients may be more vulnerable to posttraumatic stress disorder (PTSD), with depressed FM patients having a three-fold increase in PTSD compared to those with chronic fatigue only [41]. Breast implants, at one time implicated in FM, are not associated with FM [42,43]. Similarly, cigarette smoking has been associated with more severe FM symptoms, rather than FM per se, and should be discouraged for global health reasons [44].

Recommendations:
1. Fibromyalgia, a condition that can wax and wane over time, should be diagnosed in an individual with diffuse body pain that has been present for at least 3 months, and who may also have symptoms of fatigue, sleep disturbance, cognitive changes, mood disorder, and other somatic symptoms to variable degree, and when symptoms cannot be explained by some other illness [Level 5 [2, 12, 45, 46], Grade D].

1.2 What physical abnormalities may be present in fibromyalgia?

The physical examination, specifically musculoskeletal and neurological, is usually within normal limits except for tenderness of soft tissues. Soft tissue tenderness can include pain report on examination of the tender points, however, as described in the 2010 ACR diagnostic criteria, specific tender point count is no longer required for a diagnosis of FM [2].

Sensitivity to light touch, interpreted as dysaesthesia or touch allodynia (unpleasant sensation or pain after a non-painful stimulus), may occur, but without other objective neurological findings. Expression of pain or pain behaviours may be present but should not imply faking of symptoms [47].

1.2.1 The tender point examination

The tender point examination has been widely disputed as an objective test in FM [48-56]. Embedded in the diagnostic criteria established for research purposes and not applicable to an individual patient in clinical practice, the 1990 ACR criteria for a diagnosis of FM required 11/18 tender points to be present in designated areas [1]. These points, located at soft tissue sites, reflect a reduction in pain threshold without underlying tissue pathology and show variable reliability [57, 58]. Reduced pain threshold has also been documented by application of a pneumatic tourniquet cuff [59]. The weight
attributed to the tender point examination has detracted from the global concept of FM and was thus revisited in the new 2010 ACR criteria [60].

The correct examination method for tender points, which can be performed by digital palpation, myalgic scoring or dolorimetry has also been debated, with digital examination most commonly used [61]. The presence of tender points may even associate more with distress rather than as an indicator of pain [62]. Examination of even a few selected points may be sufficient to identify FM [63]. Tender points may even be faked, but truly bear no consequence to the composite of suffering of FM [64].

The new criteria for a diagnosis of FM, with the elimination of the tender point examination, perform well in identifying patients with a previous diagnosis of FM [2]. A recent German working group has concluded that FM can be diagnosed for clinical purposes on the basis of symptoms without a tender point examination [65].

Recommendations:
2. All patients with a symptom complaint suggesting a diagnosis of fibromyalgia should undergo a physical examination which should be within normal limits except for tenderness on pressure of soft tissues (ie. hyperalgesia which is increased pain following a painful stimulus) [Level 4 [2, 3, 66], Grade D].

3. Examination of soft tissues for generalized tenderness should be done by manual palpation with the understanding that the specific tender point examination according to the 1990 ACR diagnostic criteria is not required to confirm a clinical diagnosis of fibromyalgia [Level 5 [1, 2], Grade D].

1.3 What investigations should be done in a patient presenting with widespread pain?

No laboratory investigation confirms a clinical diagnosis of FM and unnecessary investigations which may be detrimental to patient well-being should be avoided. FM is not a diagnosis of exclusion [67]. Simple laboratory testing should be limited to a complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), thyroid stimulating hormone (TSH), and creatine kinase to rule out conditions that can present similarly to FM. These may include endocrine disease (hypothyroidism),
rheumatic conditions (early inflammatory arthritis or polymyalgia rheumatica) or neurological disease (myopathy, or multiple sclerosis), depending upon the clinical evaluation. Appropriate additional testing, which might include referral for sleep evaluation, or formal psychological evaluation may be required in selected patients.

Reduced levels of vitamin D or vitamin D supplementation have no effect on pain in FM [68-70]. A positive antinuclear antibody (ANA) in low titre, present in 8-11% of FM patients, similar to healthy controls, does not predict future connective tissue disease [71-
73]. As no consistent abnormality has been identified in immune function, any screening should only be driven by clinical findings [74-76].

Recommendations:
4. Fibromyalgia 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, erythrocyte sedimentation rate
(ESR), C-reactive protein (CRP), creatine kinase, and thyroid stimulating hormone (TSH). 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 [75, 76], Grade D].

1.4 How should the diagnosis of fibromyalgia be confirmed?

The responsibility for the diagnosis and management of FM should be shifted away from the specialist and concentrated in the primary care setting. Specialist confirmation or fulfilling diagnostic criteria is not required [1, 77-79]. Most physicians rely on a combination of symptoms and normal blood testing to diagnose FM with less than 10% using criteria [80]. Questionnaires used in the research setting are also not clinically useful in daily practice [81].

Early diagnosis will avoid lengthy, costly and unnecessary investigations, a cause for patient uncertainty that will prolong healthcare behaviours and foster medicalization [6, 82, 83]. An early diagnosis will allow attention to be focused towards symptom management, attainment of optimal health and maintenance or improvement of function.

New symptoms should be evaluated on merit. Seldom does FM herald some other disease with only 2 of 91 patients developing some other condition over a 4 year period [84].

Recommendations:
5. The primary care physician should establish a diagnosis of fibromyalgia 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[6, 77, 82, 83], Grade D].

1.5 Is there a role for application of diagnostic criteria for an individual patient?

The concept of FM was initially crystallized by the American College of Rheumatology (ACR) in 1990, and was further revised in 2010, taking into account symptoms other than pain, as well as the questionable value of the tender point examination [1, 2]. FM represents a spectrum of symptoms which fluctuate in intensity, although the underlying condition persists [58, 66, 85]. These criteria were developed to identify patients for research study and not for application to an individual patient in the clinical setting. A modification of the original 2010 ACR criteria requires that the questionnaire be entirely completed by the patient, without need for additional physician questionning, simplying the tool (Appendix D).

Recommendation:
6. The ACR 2010 diagnostic criteria for fibromyalgia can be used at initial assessment to validate a clinical diagnosis of fibromyalgia with theunderstanding that symptoms vary over time [Level 3 [1, 2, 58], Grade B].

1.6 What conditions can present similarly to FM?

A number of conditions may present similarly to FM, and may be identified by a
thorough clinical evaluation. Diagnoses that can be confused with FM may be grouped into the following categories: musculoskeletal, neurological, psychiatric/psychological and drug related [76].

Although patients with an early stage of an inflammatory rheumatic condition such as rheumatoid arthritis, inflammatory spondyloarthritis, systemic lupus erythematosus, polymyalgia rheumatica or myositis may have generalized body pain, identifiable physical or laboratory abnormalities will develop over time [86, 87]. The presence of a single abnormal laboratory test such as a positive rheumatoid factor, positive ANA, or raised ESR is not evidence alone for the presence of a connective tissue disease [71, 72]. Myofascial pain syndromes tend to present with more localized pain and are associated with “trigger points” [88].

Neurological conditions with body pain include multiple sclerosis, neuropathies, with pain more specifically localized, and myopathies [87]. Hypothyroidism should also be remembered as a condition that may present with ill-defined pain and fatigue. Depression can present with pain, although local tenderness is more common in FM patients compared to those with depression [89].

FM may develop after an infectious illness, most commonly viral, but a search for an infectious aetiology is not routinely required. Infectious diseases such as Lyme disease, hepatitis C infection, and human immunodeficiency disease may have symptoms mimicking FM, but any testing in this regard should be dependent upon a clinical suspicion of these infections [90, 91]. Medications such as lipid lowering agents in the category of statins, aromatase inhibitors used to treat breast cancer and bisphosphonates for the treatment of osteoporosis and bone metastases may cause body pain [92-94].

FM may occur concomitantly with other medical, neurological or rheumatologic illnesses [76]. Recognition of the co association of FM may influence treatments. For example, a patient with rheumatoid arthritis, in the absence of inflammatory activity, may experience pain due to FM.

Recommendations:
7. Healthcare professionals should be aware that some medical or psychological conditions may present with body pain similar to fibromyalgia, and patients with other medical illnesses may have an associated fibromyalgia [Level 5 [76, 86, 87, 90, 91], Grade D].

1.7 What is the recommended patient trajectory?

Delay in diagnosis of FM may be attributed to poor recognition of FM by patients and healthcare professionals, with adverse effect on health and considerable healthcare and personal costs [5, 6, 95]. Patients with FM will first present to a primary care physician and ideal care should remain in the primary care setting without any clear advantage for care by a specialist [77, 78, 96, 97]. Whether a diagnosis of FM is advantageous from the pharmacoeconomic perspective remains debatable with reports of both increased as well as reduced healthcare utilization and costs [6, 98]. Education and improved knowledge translation will reassure healthcare professionals to diagnose and manage persons with FM more effectively.

Specialist consultation should be reserved for patients with atypical symptoms which might suggest an alternate diagnosis and is not required to confirm a diagnosis of FM [97, 99]. In selected cases referral for sleep evaluation or psychological consultation may be indicated. No advantage was observed when patients were followed in a specialist setting compared to primary care [97].

Although care in a multidisciplinary setting may be desirable, this is not realistic for most patients [100]. Multidisciplinary teams may include nurses, physiotherapists, kinesiologists, social workers and psychologists amongst others. Nursing support for FM patients has been underutilized, can provide a valuable contribution to patient care and can reduce waiting time to consultation and increase patient satisfaction [101]. Nursing
care can help the patient identify realistic outcome goals and focus towards attaining optimal health [102]. Public education will also facilitate an earlier diagnosis and promote the belief that FM patients are best managed in the primary care setting.

Recommendations:
8. Management of persons with fibromyalgia should be centered in the primary care setting with knowledgeable healthcare professionals, and ideally, where possible, this care may be augmented by access to a
multidisciplinary team [Level 1 [96, 97], Grade A] or team member to provide support and reassurance [Level 3 [101, 102], Grade C].

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 those patients
who have failed management in primary care or have more complex comorbidities [Level 5 [77], Grade D].

1.8 How can prejudice and scepticism regarding the validity of fibromyalgia be countered?

Knowledge that FM is grounded in neurophysiological mechanisms will reduce
scepticism regarding a syndrome of subjective complaints. Physician comfort with a biomedical paradigm which prioritizes diagnostics adds to the insecurity in management of these patients, with some authors contending that the label of FM promotes poor health [103-105]. Patient preoccupation with physical symptoms rather than developing control over illness invokes frustration for the healthcare professional and erodes a good
therapeutic relationship [106]. The construct of somatization has however never been validated in situations involving pain, and particularly in FM. In contrast, patients with FM report frustration with healthcare professionals, dissatisfaction with the clinic visit and seek a concrete somatic diagnosis [107, 108]. Although discordance between patient and physician assessment of health perceptions has been reported, physicians have expressed the desire to comply with patients’ wishes and avoid frustration [103, 108].
When physicians prejudge FM patients in moralising terms and believe them to be illness-focused, demanding and medicalized, the patient doctor alliance will be eroded with adverse effect on patient outcome [109]. Both the individual patient’s concept of illness as well as perceived attitudes of the healthcare team impacts on global well-being. Shared decision-making between patient and physician can improve the quality of interaction [110]. An early diagnosis may have pharmacoeconomic implications with reduced healthcare costs as measured by fewer investigations, less referral to specialists and reduced healthcare visits [6, 83].

Recommendation:
10. In caring for persons with fibromyalgia, healthcare professionals should be educated regarding the pathogenesis of fibromyalgia [Level 5, Consensus], empathetic, open, honest, should not demonstrate negative attitudes, and should practice shared decision-making [Level 3 [106, 107, 110], Grade D].

1.9 What causes fibromyalgia and how is this condition explained in physiological
terms?

Although the cause of FM is unknown, understanding that neurophysiological changes present in FM will reassure healthcare professionals that this condition is valid. An elementary appreciation but not in-depth knowledge of neurophysiological mechanisms will also help towards treatment choices. Neurophysiologic testing remains in the research domain and is not currently available for routine patient care, nor should be required to confirm a diagnosis of FM.

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 (HPA) axis stress-response system. Documented abnormalities include evidence of peripheral sensitization and wind-up phenomenon, central sensitization with changes in functional MRI and SPECT scans of the brain, increased levels of substance P in the cerebrospinal fluid, and impairment of descending noxious inhibitory control (DNIC)
[111-118].

Familial studies point to some genetic predisposition with up to 26% of relatives of patients with FM reporting chronic widespread pain (CWP), and FM diagnosed in 28% of offspring of FM women [119, 120]. Genetic factors may predispose some individuals to a dysfunctional stress response via the HPA axis [121]. While no individual gene has been associated with FM, there is increasing evidence of a polygenic effect, with polymorphism of genes affecting serotoninergic, catecholaminergic and dopaminergic systems playing a role [122, 123].

Psychosocial distress has been shown to predict onset of chronic widespread pain in population studies conducted in England [124, 125]. Early life adversity is linked to chronic widespread pain in adult life [126]. Abuse, which may have been sexual, physical or psychological, particularly in childhood has been reported with greater frequency in FM patients than controls [127-129]. These numerous interacting factors may be the
setting in which a stressful event, which could be physical such as a viral illness, traumatic, or psychological, can lead to a vulnerable health status and may be a trigger for FM as reported for nearly a quarter to a third of persons with FM [130].

Recommendations:
11. Healthcare professionals should be knowledgeable that objective neurophysiologic abnormalities have been identified in patients with fibromyalgia in the research setting, but are not available in clinical practice for either the diagnosis or care of persons with fibromyalgia [Level 5 [111, 117], Grade D].

12. Patients and healthcare professionals should acknowledge that genetic factors as well as previous adverse events may have contributed to the development of fibromyalgia, but focusing excessively on a triggering event could compromise patient care and should therefore be discouraged [Level 5 [123, 126, 130], Grade D].

1 Division of Rheumatology, McGill University, Montreal, Quebec, Canada
2Alan Edwards Pain Management Unit, McGill University Health Center, Montreal, Quebec, Canada
3Faculty of Law, Université de Montréal, Montreal, Quebec, Canada
4Division of Rheumatology, Tufts University School of Medicine, Boston, Massachusetts, USA
5Department of Family Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
6Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
7Centre de la recherche du Centre hospitalier de l’Université de Montréal; Department of Anesthesiology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
8Division of Physiatry, University of Toronto, Toronto, Ontario, Canada
9Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, London, Ontario, Canada
10Patient representative