The Clinical Concept of Fibromyalgia As a Changing Paradigm in the Past 20 Years

The Clinical Concept of Fibromyalgia as a Changing Paradigm in the Past 20 Years

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Abstract functional impairment [2]. The clinical concept of FMS was initially described by Yunus and colleagues and Fibromyalgia (FMS) is a valid clinical condition that affects crystallized by the publication of the 1990 American 2%–4% of the population with a pivot symptom of College of Rheumatology (ACR) criteria for the widespread body pain. The cause and cure of FMS are as classification of FMS [3, 4]. yet unknown. The concept of FMS has evolved over the past two decades to incorporate symptoms beyond pain An evolution of the clinical understanding of FMS over the as contributing to the global spectrum of suffering. FMS is last two decades has emphasized the importance of now recognized to be grounded in the neurological symptoms beyond pain which form an integral part of this domain with evidence of dysregulation of pain processing. condition and contribute to global suffering. In this Appreciation of the neurophysiologic mechanisms context, it became necessary for the criteria for a operative in FMS has contributed to rational treatment diagnosis of FMS to be reevaluated. The coming of age of recommendations, although a “gold standard treatment” FMS was heralded by the publication of updated criteria does not currently exist. Ideal treatments for FMS for the diagnosis of FMS, taking into consideration patients should be individualized with emphasis on active additional symptoms that are present to a variable degree patient participation, good health practices, and in individual patients [5]. In addition, the new concept of multimodal intervention, incorporating nonpharmacologic FMS recognizes that symptoms are not an all-or-none and pharmacologic treatments. Predictors of outcome, phenonemon, but can be expressed with varying severity which is favorable in over 50% of patients, are unknown, with periods of waxing and waning [6]. but those with better outcome do more physical activity and use fewer medications. Neurophysiological studies have contributed to the acceptance of FMS as a valid condition. Demonstration of 1. Introduction objective changes in the research setting has given clinicians the confidence to acknowledge a condition that 1.1. The Coming of Age after 20 Years presents with only subjective complaint and no objective Fibromyalgia (FMS) is a condition characterized by the clinical findings [1]. Dysregulation of pain processing has pivot symptom of pain throughout the body, and with been demonstrated at various levels in the nervous abnormality centered in the nervous system [1]. Over the system, but we still lack an objective test in the clinical past 20 years, knowledge regarding both the clinical as setting to confirm a diagnosis or gauge response to well as the neurophysiological basis for this condition has treatments [1, 7]. However, this is no different than other accumulated. FMS affects 2%–4% of populations well-recognized conditions, for example, irritable bowel worldwide and is a cause of considerable suffering and syndrome (IBS), migraine, and depression. It is undeniable that depression is a serious condition and yet it lacks an Beginning with their landmark study in 1981, Yunus and objective test. coworkers have championed the recognition of this condition over the past three decades [3]. In this paper, Even with objective scientific support of abnormality, the authors emphasized that FMS is more than pain, some skepticism still exists regarding the validity of adding many other symptoms or associated conditions, subjective complaints requiring complete reliance on the for example, fatigue, stiffness (which is a prominent practice of the art of medicine [8]. The controversy symptom in some patients), poor sleep, morning fatigue, regarding the existence of this syndrome should now be tension-type headache, migraine, IBS, subjective swelling put to rest. Efforts should be directed towards better (which often leads to a misdiagnosis of rheumatoid understanding of the neurophysiological abnormalities, arthritis), subjective numbness, anxiety, stress and improved clinical recognition of patients, and translation depression, as well as modulating factors of pain and of mechanistic studies into optimizing treatments. In this stiffness [3]. paper, we will present current concepts of FMS, which can be applied to the rational management of these There have been physicians who have disputed the patients. This paper will address current concepts and validity of a condition presenting with subjective challenges pertaining to the clinical understanding of complaints and associated with considerable functional FMS. impairment, without objective clinical findings. Some have even suggested that FMS was mostly a 2. Methods manifestation of depression [12, 13]. However, This paper is based on a review of the literature achieved depression and FMS are biologically two different by a comprehensive literature search using MEDLINE, diseases, including an absence of central sensitization in CINAHL, Cochrane, PUBMED, EMBASE, Cochrane Library, depression by almost all stimuli [14, 15]. and PsycINFO. MEDLINE is widely used as a premier The clinical challenge of this condition remains as there is source for biographic coverage of the literature and the still no objective clinical finding or test to confirm the CINAHL for nursing literature. In addition to the formal diagnosis, or gauge severity of symptoms. Physicians are search, a manual search from the references cited by required to assess this syndrome on the basis of original studies and reviews was also used where subjective report only. This has fostered a sense of clinical indicated. uncertainty leading physicians to often consider a 2.1. The Clinical Challenge Remains diagnosis of FMS only when other possible diagnoses have been excluded [16]. This insecurity by health care Clinicians are traditionally skeptical of any condition professionals may be a factor leading to frequent use of wherein there is disconnection between complaint and unnecessary investigations and can contribute to physical examination findings. This was first evident with excessive medicalization of patients. It has been clearly the construct of phantom limb syndrome, now accepted documented that a definite diagnosis of FMS leads to as a real phenomenon and cause of pain in the absence of reduced health care use and also better global patient anatomical tissue in the periphery [9]. Beginning in the health [17, 18]. 1980's, there were emerging reports that body pain, in the absence of tissue damage, could be present [3, 10, 2.2. Fibromyalgia Is More Than Just Pain 11]. These patients were mostly referred to Initially, FMS was considered to be a condition of pain, rheumatologists in order to rule out some connective and this concept was reinforced by the 1990 ACR criteria tissue disease. The notion that FMS is indeed a true entity which only included features of pain and localized body follows publication of neurophysiological studies attesting tenderness [4]. The understanding of FMS today to objective findings in a clinical condition that was often acknowledges that patients with FMS will have a perceived to be nebulous. symptom complex characterized by more than just pain with other complaints present with variable intensity [19]. Besides those mentioned above, that is, fatigue, sleep disturbance, cognitive changes, and mood disorder, other FMS patients can experience important cognitive symptoms or associated conditions include restless legs dysfunction, which associates with pain, but not current syndrome, periodic limb movements in sleep, depression or anxiety, and includes poor working temporomandibular disorder (TMD), multiple chemical memory, spatial memory alterations, free recall, and sensitivity, and interstitial cystitis [20, 21]. Each of these verbal fluency [30–32]. Cognitive symptoms are present in symptoms plays a variable role in the presentation of an FMS even after adjusting data for age, medications, individual patient and all contribute to a greater or lesser education, and depression [31]. Cognitive changes were degree towards the overall effect of impaired quality of however no different when compared to other pain life and reduced functional activity. patients, suggesting that pain per se may affect cognition [33]. Although most patients experience associated The typical patient is female in her 40's or 50's with a few symptoms in varying degree, it is not required that these years of ill-defined musculoskeletal pain [22]. Onset of be present for a diagnosis of FMS. symptoms is usually gradual, but occasionally there may be a sudden onset following an identifiable event, such as Patients with FMS are heterogeneous and attempts have a medical illness, a mentally stressful incident or physical been made to group patients into categories to help trauma. Only 5–7% of the FMS patients are males. The direct treatments and predict outcome [25, 34, 35]. clinical characteristics of FMS among men are similar to Subgrouping of patients with FMS according to those in women, except that men have fewer symptoms, psychological distress, depression in particular, has been fewer pain sites, less frequent fatigue and IBS, and fewer most commonly reported, but longitudinal studies using tender points [23]. subgroups to direct treatment and predict outcome are still required. In a recent analysis of over 3000 patients in Pain is described as being diffuse, deep, and continuous various clinic settings in Germany, patients could be often with periods of exacerbation. Pain symptoms may subgrouped into 5 categories depending upon pain be modulated by various factors including psychological characteristics and associated comorbidity of depression stress, excessive physical activity, fatigue, or changes in [25]. It is however still premature to attempt to categorize the weather [24]. Some patients also report a superficial patients in the clinical setting, other than to pay particular burning quality to pain with increased sensitivity to attention to psychological status. painful stimuli-termed hyperalgesia, and may also have features of allodynia or pain following an innocuous FMS may accompany other medical, neurological, or stimulation such as touch [25]. Pain quality or rheumatologic illnesses as a comorbid condition [36]. unpleasantness is an equally important component of the Conditions that have been associated with FMS include pain experience, but is not commonly measured either in amongst others various rheumatologic conditions such as clinical practice or even in the study setting of patients systemic lupus erythematosis and rheumatoid arthritis as with FMS. well as neurologic disorders such as multiple sclerosis and postpolio syndrome [36, 37]. It is important to appreciate Multiple symptoms contribute to the burden of suffering that FMS can coexist with these conditions in order to and are increasingly recognized as important from the direct treatment appropriately. For example, a continuous patient perspective and require attention for achieving complaint of pain due to FMS in a patient with optimal patient care [5, 19, 26]. Nonrestorative sleep is rheumatoid arthritis would be incorrectly treated by associated with widespread pain [27]. Many components increasing treatments with disease modifying agents, of sleep have been measured as abnormal in FMS patients rather than addressing the symptoms associated with including sleep latency, sleep disturbance, and impaired FMS. daytime functioning [28]. Poor quality and duration of sleep has been shown to have a negative impact upon 2.3. The Conundrum of Criteria for Diagnosis of fatigue and affect [29]. Other sleep disorders such as Fibromyalgia restless leg syndrome or sleep apnea may also occur in patients with FMS. Criteria for the classification of FMS were established almost two decades ago and take into account only the symptom of pain [4]. Although the cardinal symptom of that tender points can be faked, and that they truly bear FMS remains pain, symptoms of fatigue, sleep no consequence to the composite of suffering of FMS. disturbance, cognitive changes, mood disorder, and other somatic symptoms contribute to the complexity of this Taking into account the presence of symptoms other than syndrome [19]. pain and the questions posed by tender points, new criteria for a diagnosis of FMS have recently been The original 1990 criteria for classification of FMS pose at published [5]. These new criteria, which may be viewed as least 2 important practical problems [4]. Firstly, they were complementary to the 1990 criteria, with the elimination developed specifically for the purpose of identifying of the tender point examination, perform well in patients for further research in this condition, and identification of patients with a previous diagnosis of FMS secondly, they addressed only the complaint of pain by [5]. The new criteria therefore have included other means of a report of pain and examination of tender symptom domains and made them an essential part of points. These criteria were often erroneously used to the criteria set. However, elimination of tender points validate a diagnosis in individual patients in the clinical also decreases specificity. Thus, unlike the 1990 ACR setting and did not take into account any other criteria, the new 2010 criteria require exclusion of other concomitant symptoms or severity of symptoms. conditions causing pain. Further, these criteria have not been validated in primary care setting. A recent German According to the 1990 criteria for a classification of FMS, working group has concluded that FMS not only can be in addition to widespread body pain, tender points were diagnosed for clinical purposes on the basis of symptoms required to be present in at least 11/18 designated areas without a tender point examination, but may also be [4]. Tender points are located at soft tissue sites and established using the old 1990 ACR criteria [46]. reflect a reduction in pain threshold without underlying Therefore, wisdom suggests that a clinical diagnosis of tissue pathology. Tender points have elicited considerable FMS today should not be dependent solely upon a debate and their true value has been questioned. Tender subjective count of tender points, but physicians may point examination is a subjective test, open to individual continue to use them for the present time in order to help interpretation and reflects an overall reduction in pain solidify a diagnosis, as well as diagnosis of concomitant threshold, rather than a pathological process at the soft diseases, including depression [44, 47]. tissue site [38]. They may be present in normal individuals and can increase with age. Reliability is variable, ranging 2.4. Fibromyalgia Is No Longer a Diagnosis of Exclusion from good to poor [39, 40]. The association of pain report and tender point count is however poorly correlated, As early as 1989, Yunus has advocated that a diagnosis of suggesting that these measurements represent different FMS should not be made by exclusion, but rather by parameters of pain experience in FMS [41]. positive assessment of a constellation of symptoms [48]. Additionally, this clinical diagnosis should be made in the The correct examination method for tender points is also primary care setting without need for excessive and costly debatable. Methods that have been used include digital investigation or repeated specialist referral [16]. A palpation, myalgic scoring, or dolorimetry [42]. Although detailed medical history and good physical examination digital examination is the most commonly used method of can be used to exclude other rheumatologic conditions [8, assessment, it is often not used by physicians caring for 49]. FMS patients [5]. There is also report of poor concurrent validity when tender points were examined digitally or by Primary care physicians will be the first to evaluate and dolorimetry [43]. A person's current psychological state manage patients with a complaint of body pain due to has been shown to influence measurement of tender FMS [16, 50, 51]. Family physicians are likely best suited points suggesting an association with distress rather than for the care of these patients in view of the multiplicity of an accurate indicator of pain [44]. It has even been complaints and need for therapies that span many suggested that the examination of a few selected points categories [16]. It is also questionable whether there is may be sufficient to identify FMS [45]. It is also argued truly a need for the diagnosis to be confirmed by a medical specialist such as a rheumatologist. The value of specialist opinion should be for the patient in whom some Although the exact cause of FMS is unknown, other condition requires exclusion, rather than to confirm abnormalities of nervous system pain processing can the diagnosis of FMS. plausibly explain the persistence of pain in the absence of tissue damage [58]. The reason for this dysregulation is The clinical presentation of FMS can however be quite likely dependent upon a number of interacting factors, diverse with some areas of the body more painful than which include genetic predisposition, neurophysiological others, fluctuations in intensity of pain and variable changes, and abnormal stress response. As following intensity of other associated symptoms. Patients also articles in this publication will elaborate further on differ considerably in terms of severity of functional pathogenesis, we will provide only a brief overview. impairment [52, 53]. This awareness of differences in presentation and heterogeneity of FMS is increasingly 3.1. Genetic Factors appreciated and is helpful to the clinician. The evidence for genetic predisposition stems from It is also time to dispel the fallacy that FMS is a primary studies showing familial aggregation of FMS [59, 60]. The psychogenic condition. As mentioned earlier, depression odds ratio for a diagnosis of FMS was reported as 8.5 for a and FMS are biologically different conditions and patient with a first-degree relative with FMS compared to depression is present in any chronic diseases, including having a relative with rheumatoid arthritis [60]. Familial those with organic pathology, such as cancer and aggregation should be a clue for some genetic coronary artery diseases. There is no question that the contribution, but does not concretely prove a genetic link, psyche and the body are tightly linked. Illness, particularly as factors such as environment or a triggering event need prolonged and poorly recognized, fosters mood to be taken into consideration. Candidate genes disturbance. Conversely, mood disorder is associated with implicated in FMS include those controlling serotonin reduced motivation to be physically active, resulting in mechanisms, dopamine receptors, as well as metabolism muscle deconditioning and subsequent pain complaint. of catecholamines [7, 61]. FMS patients have a greater prevalence of lifetime as well as current mood disorder compared to other populations, 3.2. A Vulnerable Psychosocial Setting but this should not be viewed as causative in each and Psychologic and stress-related factors are the second area every patient. It is possible that a vulnerable psychological of consideration regarding pathogenesis of FMS. Up to status may predispose an individual to onset of a pain 40% of patients' report the onset of symptoms preceded process, particularly if triggered by some event [54–56]. by some triggering event, which might be either A clinical evaluation can be used to exclude most other psychological or physical [62]. An abnormal physiological conditions that could masquerade as FMS [49, 57]. Some response to a stress mechanism could explain this common medical conditions that should not be missed in phenomenon [54–56]. Impairment of the stress response, a patient presenting with chronic widespread pain include as measured by hypothalamo-pituitary-adrenal (HPA) axis hypothyroidism, statin-induced myopathy, and response, was identified prior to the onset of chronic polymyalgia rheumatica, especially in the older patient. widespread pain in a prospective population-based study These are familiar to primary care physicians and should in England [63]. Psychological factors therefore play an not cause confusion. Of greater concern is that a diffuse important role in neurophysiological responses and have pain syndrome may either herald or mask a treatable even been shown to affect changes at the spinal level rheumatologic condition such as rheumatoid arthritis, [64]. systemic lupus erythematosis, or a neurological illness Although FMS patients have a greater lifetime frequency such as multiple sclerosis, although this has only rarely of depression [65], depression per se appears not to be a been recorded in a few prospective studies. direct causative factor in the pathogenesis of FMS [66]. Psychological symptoms, of which depression and anxiety are the most common, are however present in between 3. What Causes Fibromyalgia? 30 and 80% of FMS patients and contribute to poor global Finally, as patients with FMS commonly report sensitivity health [66]. to medications, clinical experience suggests that low doses of medications can be used, with gradual increase 3.3. Neurophysiological Changes in dose depending upon efficacy and tolerability. It is the The concept of a neurological versus a purely somatoform authors' experience that doses of medications used in real disorder to explain the pathogenesis of FMS continues to life clinical practices are often much lower than those stimulate debate [1, 67]. There is however convincing reported in industry-controlled studies. It is also notable documentation of changes at various levels of the nervous that many of the adverse effects of medications present system supporting an abnormality that is primarily symptoms similar to those experienced by patients with neurogenic and will be further elaborated in ensuing FMS. Therefore, any patient being treated with a articles in this supplement. A recent development in the medication should be carefully evaluated for both efficacy pathophysiology of FMS is that it is characterized by as well as side effects, and medications should be central sensitization (CS), well documented in the discontinued unless there is evidence for definite benefit. laboratory setting [20, 21, 68]. CS also binds FMS to other In addition, combinations of medications are also more similar syndromes, for example, IBS and TMD, collectively commonly used in practice, although there is limited known as central sensitivity syndromes [20, 21]. evidence to support this practice from randomised clinical trials. Chronic pain, as occurs in FMS, may be perpetuated by numerous interacting mechanisms, including increased A key principle to management of patients with FMS is to excitation or reduced inhibition [58, 69]. Neurophysiologic encourage a shift of focus of control towards the patient studies have demonstrated evidence of dysfunctional and to ensure that the patient is an active rather than a central pain mechanisms including spinal hyperexcitability passive participant in management. Understanding and [68, 70], changes in thalamic and cortical pain matrix, as support should form the cornerstone of care for these well a grey matter volume [71, 72], and impaired function patients, with treatment strategies directed towards of normal descending inhibitory mechanisms [73, 74]. In psychological status and physical symptoms within the simple terms, there is evidence for excessive pain-related context of family and society. Most patients will neuronal activity at multiple levels of the central nervous eventually with time find some treatment modality which system, structural, and functional changes in the brain by will at least somewhat modulate, but not cure symptoms, imaging studies and impaired function of normal improve health status globally and improve function. descending inhibitory mechanisms. Evidence-based treatment guidelines include those 4. Treatment Challenges developed by the American Pain Society (APS) in 2005 and the European League Against Rheumatism (EULAR) in Treatments will be fully addressed in another article of 2008 [49, 78]. Recent reviews of treatment options state this supplement. We will however provide a brief that there is good to moderate evidence for efficacy of introduction by emphasizing new concepts that apply to over 20 treatment interventions in FMS, highlighting the management of FMS. Firstly, the concept of symptom- uncertainty in management of these patients [79]. based treatments is logical and will allow a focussed Approval of several drugs by the FDA in recent years, for starting point for a physician. Secondly, in the setting of example, pregabalin, duloxetine, and milnacipran, has no single “gold standard” treatment, a multimodal been of great help in alleviating symptoms. Other approach which includes both nonpharmacologic and medications may also be used [77]. pharmacologic treatments is rational [75–77]. In this regard, patient education with emphasis on an active role Nonpharmacologic treatments are an important of the patients is critical. A patient-centred approach with component of management and recommended in both individualization of management is very important. sets of guidelines. These might include a tailored exercise program, water therapy, physiotherapy, relaxation, cognitive behavioural training, and psychological support severity of symptoms. Therefore, the accurate recognition [80]. of FMS and assessment of response to treatments still require the time-honoured art of clinical medicine [85]. 5. Outcome Is Not Universally Bleak There is currently no cure for FMS, and no single Factors that can help predict the outcome for patients treatment is universally effective for control of pain and with FMS are as yet not fully understood, but patients the associated features of this condition. Even in the that do well are more likely to be engaged in physical absence of complete understanding of cause and activity and use less medication. Realistic outcome goals pathogenesis, treatments can be directed to alleviate should be emphasized. Reduction of symptoms should be symptoms with the goal to improve functional status. translated into improved functional status. When a Global outcome with attention to overall well-being patient reports improvement in symptoms without a represents a more realistic outcome measure that is both parallel functional change, the physician should question clinically applicable and pertinent to the patient. The first the true efficacy of the treatment, secondly the side translation of the knowledge of the pathogenesis of FM effect profile which might be contributing to poor effect has however greatly facilitated introduction of treatment on function, and finally patient motivation to achieve an options, including use of pharmacological agents, that are improved health status. finally beginning to show promise for the management of this illness. A study of outcome done by postal questionnaire in the USA suggested continued pain and disability, with little References change over time [52, 53]. However, publications from 1. Perrot S, Dickenson AH, Bennett RM. 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