Classification, Epidemiology, and Natural History of Fibromyalgia

Kevin P. White, MD, PhD, and Manfred Harth, MD

Address Department of Medicine, University of Western Ontario, K289, 268 Grosvenor Street, P.O. Box 5777, London, Ontario N6A 4V2, Canada. E-mail: kevin.white@sjhc.london.on.ca Current Pain and Headache Reports 2001, 5:320329 Current Science Inc. ISSN 1531-3433 Copyright 2001 by Current Science Inc.

Fibromyalgia (FM), also known as fibromyalgia syndrome (FMS) and fibrositis, is a common form of nonarticular rheumatism that is associated with chronic generalized musculoskeletal pain, fatigue, and a long list of other complaints. Some have criticized the classification of FM as a distinct medical entity, but existing data suggest that individuals meeting the case definition for FM are clinically somewhat distinct from those with chronic widespread pain who do not meet the full the FM definition. Clinic studies have found FM to be common in countries worldwide; these include studies in specialty and general clinics. The same is true of general population studies, which show the prevalence of FM to be between 0.5% and 5%. Knowledge about risk factors for FM is limited. Females are at greater risk, and risk appears to increase through middle age, then decline. Although some authors claim that an epidemic of FM has been fueled by an over-generous Western compensation system, there are no data that demonstrate an increasing incidence or prevalence of FM; moreover, existing data refute any association between FM prevalence and compensation. Claims that the FM label itself causes illness behavior and increased dependence on the medical system also are not supported by existing research. This article reviews the classification, epidemiology, and natural history of FM.

account for between 14% and 17% of work loss days [11]. In economically developing countries, the prevalence of MSK pain may be even higher, affecting 24% to 31% of adults in Indonesia [12] and 36% of respondents in Thailand [13]. Fibromyalgia (FM), also known as fibromyalgia syndrome (FMS) and fibrositis, is a common form of nonarticular rheumatism that is associated with chronic generalized MSK pain, fatigue, and a long list of other complaints [14]. Clinic studies have found FM to be common in countries worldwide, including economically developing countries such as Mexico [15], Poland [16], and Pakistan [17]. This article reviews the classification, epidemiology, and natural history of FM.

The Classification of Fibromyalgia

Controversies in classification Medicine has recognized muscular and other soft tissue pain as clinical problems for several centuries [18,19]. Gowers coined the term fibrositis in 1904 for a painful condition of muscles, which he believed to be due to inflammation [18]. Although clinical states of regional and generalized muscular pain attracted the interest of some physicians, no consistent pathologic changes could be detected, certainly none that strongly suggested inflammation. Fibrositis had become an almost forgotten entity until Smythe and Moldofsky [20] started publishing their studies. The term fibrositis was subsequently changed to that of fibromyalgia (FM) or fibromyalgia syndrome (FMS), as it became clear that inflammation in either muscle or fibrous tissue was not part of this condition [21]. At first FM seemed to meet with a friendly reception. Physicians were pleased to find that they could now label the many patients with generalized pain, fatigue, and sleep disorders that they were seeing in their practices. This honeymoon period did not last very long. The last 10 years especially have seen increasingly hostile criticism of FM. The condition affects many patients, and a veritable epidemic was said to have occurred; moreover, many of the sufferers seemed unable to work and requested disability payments [22]. FM was perceived by some as one of several functional somatic syndromes with patients mistakenly attributing abnormalities of function to a physical rather than psychological condition [23]. There are also those who think that FM does not exist [24]. Some of the

Musculoskeletal (MSK) pain is common worldwide. In economically developed countries such as the United States, between 14% and 26% of the adult population suffers from chronic pain or arthritis [1,2], approximately 11% report chronic widespread pain (CWP) [3], and MSK disorders account for 15% of work loss days [4]. The figures are similar elsewhere. In Canada, 15% of adults report chronic MSK pain [5], 7% report CWP [6], and 5% report physical disabilities secondary to MSK illness [7]. In Europe, the prevalence of chronic widespread MSK pain varies between 11% and 17% [810], and MSK disorders

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Table 1. Is fibromyalgia a distinct entity?

Arguments against 1. FM is part of CWP, there is no reason to differentiate 2. Definition of FM is tautologic, there are no gold standards 3. FM pain is psychogenic, there are no objective abnormalities Arguments for 1. Patients with FM have a higher female prevalence, and show worse function, more distress than those with CWP; even if FM is an extreme part of the CWP spectrum, it is useful to consider it separately 2. Definitions are tautologic (see dictionaries, mathematics). There are few gold standards in rheumatology 3. There are numerous neurochemical, neuroendocrine, and even imaging abnormalities; psychogenic pain is an outdated concept

CWPchronic widespread pain; FMfibromyalgia.

criticism probably reflects a sense of frustration with the slow progress made in the understanding and treatment of this condition, the absence of specific abnormalities, and the difficulties in assessing disability claims made by the patients [25]. Frustrations aside, there are nevertheless some strong criticisms, which have to be addressed. Three of these are especially important (Table 1): 1. Is it appropriate to consider FM as an entity that deserves specific recognition and is distinct from CWP? 2. The definition of FM by a committee of the American College of Rheumatology (ACR) [4] involved tautologic reasoning, and no gold standards were used [26]. 3. Both the historical criteria (pain) and the physical signs (report of pain on pressure of tender points) are entirely subjective and patient-dependent without any hard evidence of underlying abnormalities. What objective changes, if any, are there to support the existence of FM?

A distinct entity or part of a spectrum? Generalized MSK pain, which accounts for the great majority of cases of CWP, is a common problem with figures ranging widely between 10.6% to 17% of adult populations [27]. It should be noted that the definition for CWP differs among various studies [28]. Why should CWP be distinguished from FM? In some cases the criteria for CWP are close enough to those of FM that there seems to be little difference between the two on the basis of history alone. Do tender points then help in distinguishing them? In a well-known British study, Croft et al. [29] concluded that tender points were common in subjects with CWP, those with regional pain, and even in those with no pain. They, therefore, came to the conclusion that the combination of chronic widespread pain and high counts seemed to be one end of a spectrum of pain status and tender points. The paper is interesting but invites several criticisms: subjects were selected from two general practices, and not from a general population; one third of eligible subjects failed to reply to pain questionnaires; almost one third of the sample subjects selected did

not present themselves for further examination; and less than half the subjects who had stated on an earlier questionnaire that they had CWP still had CWP on the day of the examination, whereas 40% of those who had initially replied that they had no pain had either CWP, or regional pain at examination. The subjects examined were not typical of a general population in that two-thirds were women, and their mean age was 53 years. It is, therefore, possible that there was an unforeseen over-representation of subjects with FM in the study population, thus accounting for the observed high prevalence of tender points. Croft et al. [29,30] do not think that it is useful to use tender points to discriminate between CWP and FM. They point out that tender points correlate with high scores on the general health questionnaire, health and fatigue questionnaires, and sleep problem scores [29]. In our own studies we have found that patients with FM, ie, patients with CWP and high tender point counts, are significantly different from patients with CWP alone in terms of a higher female prevalence, more fatigue, worse function, and more distress [3133]. Our interpretation is that this really means that FM differs, at least quantitatively, from CWP. The argument really is whether FM is the extreme part of a spectrum of CWP, or whether there is a true dichotomy between CWP and FMS. Because only tender points can distinguish CWP from FM currently, it is not possible to resolve decisively this argument. We will have to wait for further evidence to decide whether there is a fundamental qualitative difference between the two. Russell [34] has argued that even if FM represents an extreme group of cases of CWP, it would still be useful to consider them separately. He has drawn the analogy of FM and CWP to other continuous variables, where an arbitrary line is drawn beyond which special consideration is given to the extreme cases; thus, he compares FM to hypertension, where blood pressure is the continuous variable in the population but where the designation hypertension is a useful marker in terms of determining current or potential morbidity. Indeed, those patients we now classify as having FM clearly seemly seem to be worse off than patients who have CWP but not FM [3133]. We, therefore, think that it is appropriate at this stage to consider FM as a separate syndrome from that of CWP.

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Fibromyalgia

The problem of tautology A committee of the ACR used a tautologic approach to adopt the criteria currently used to designate an individual as having FM. Some have deemed this inappropriate [26]. There is no question that ACR committees, which deal with classification criteria for various rheumatic disorders, use a tautologic approach because that is the best available approach for this form of study. These committees usually consist of physicians who are deemed to be experts on a certain condition, as well as statisticians and clinical epidemiologists. The clinical experts then submit to the committee a number of cases from their practice, and the committee tries to select those common clinical and/or laboratory features that have high sensitivity and high specificity. The object of the exercise is to allow physicians and other scientists to communicate with each other using a common language. The tautology involved is similar to that seen in dictionary definitions of words, or in mathematics. ACR committees have functioned in this manner to define other entities, such as rheumatoid arthritis, without any protest [35]. It is unfortunately true that the ACR committee that defined FM did not have any gold standards [21]. However, the same is true of the committees that defined rheumatoid arthritis and many other rheumatic conditions; gold standards unfortunately seem to be scarce in rheumatology. It is also true that the criteria for FM are called classification criteria; this implies that such criteria need only be applied in scientific communication; it is not clear why the ACR seems to avoid, as a rule, the term diagnostic criteria. Nevertheless, it has become common practice to use the classification criteria for purposes of diagnosis; if anything, such a practice represents adherence to higher rather than to lower standards. Is fibromyalgia imaginary? Finally, as already mentioned, there are those who deny the validity of FM, pointing out that the diagnosis is entirely based on subjective reports of pain either obtained by history, or elicited during the physical examination (tender points). Therefore, some have regarded FM as an inappropriate response to stress, a somatoform disorder, or a medicalization of the syndrome of being out-of-sorts [23,36]. Psychological abnormalities are significantly more common in patients with FM than in control populations and this will be addressed later. It is not clear whether these abnormalities precede or are the result of other distressing problems that afflict patients with FM such as pain, fatigue, and sleep disturbances. The contention that pain is a purely subjective phenomenon is increasingly difficult to accept. The contributions of central neuroplasticity to the development of pathologic pain have become well recognized [37]; abnormalities in serotonin metabolism, increased release of substance P and nerve growth factor in the cerebral spinal fluid, and several other neuroendocrine abnormalities are well documented in FM and will be

covered in upcoming sections. Even imaging abnormalities in the brain have been reported in FM thanks to the use of single photon emission computed tomography [38]. The view that FM is an example of psychogenic pain is an example of what has been termed the Cartesian dualism in pain conceptualization (the separation of mind and body), a concept that now is regarded as incompatible with the current knowledge on mechanisms of pain [39].

The Epidemiology of Fibromyalgia

Fibromyalgia in the clinic population As noted earlier, the term fibrositis seemed to disappear from the medical literature for about 50 years, but resurfaced in 1976. Now, many feel that FM has reached epidemic proportions. We now review the data to determine if it supports, refutes, or is inconclusive with respect to this apparent epidemic of FM. In 1977, Epstein and Henke [40] analyzed the results of a questionnaire that had been mailed out and completed by 826 rheumatologists practicing in the United States. They found a discrepancy in the frequency of certain conditions between university-based and community rheumatology practices: academic rheumatologists reported that tendonitis and bursitis accounted for only 5.7% of their cases, and fibrositis for 2.0%; community rheumatologists reported these diagnoses accounted for 11.6% and 6.0%, respectively. Both academic and community rheumatologists reported that degenerative joint disease and rheumatoid arthritis were the two disorders seen most commonly. Another United States survey of four community rheumatologists, which involved an audit of practice records, found FM to account for 6.1% of new cases, back syndrome for 20%, and shoulder tendonitis, bursitis, and capsulitis for 9.7% [41]. In 1981, a rheumatologist in Orange County, CA, reported on the first 1000 patients seen in his practice; as in previous surveys, rheumatoid arthritis and degenerative joint disease were the most common disorders seen; myofascial pain syndrome and psychogenic rheumatism only accounted for 4.7% and 3.3%, respectively [42]. The results of these three clinic surveys suggest that FM accounted for between 2% and 6% of rheumatology outpatients in the late 1970s and early 1980s. However, these figures contrasted with the first year in practice of a r h e u m a t o l o g i s t i n C l e ve l a n d , O H , f o r w h o m F M accounted for 16% of new patients [43]. Potential explanations for these discrepant figures include regional differences in FM prevalence, but also referral bias (variations in referral patterns for one practice versus another) and ascertainment bias (differences in the likelihood of one physician versus another diagnosing FM in a given patient). Compared to these earlier surveys, more recent rheumatology clinic surveys have generally estimated the percentage of patients with FM to be higher, between 10% and 25%; these include surveys in the United States [4447], Mexico

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[15], Spain [48], Australia [49], and Canada [50]. In the Canadian survey, FM was second only to osteoarthritis among new consults, and it was the only disorder perceived by a majority (69.3%) to have increased in frequency within the practices over the previous 5 years. FM now also appears to account for a significant percentage of patients seen in family practice clinics (2.1%) [51], general medicine clinics (5.7%) [45], and hospitals (7.5%) [52]. These most recent figures might suggest an increasing prevalence of FM in the general population, which would support claims of an epidemic. However, there are numerous significant limitations to using clinic or hospital studies to make inferences about the general population prevalence of a disorder such as FM, again including referral and ascertainment bias [53]. Increasing public and primary care recognition of FM might result in a higher proportion of individuals with CWP being referred to specialists for assessment, hence referral bias. Moreover, increasing recognition of FM likely would result in more patients with CWP being diagnosed with FM. There also may be demographic factors that influence the likelihood of being recruited into a study. For example, females are more likely than males to seek medical attention [5456]; this may explain the apparent discrepancy between the 84% to 88% female proportion of patients with FM reported in most specialty clinic surveys [57] and the 75% female proportion reported in a large general population survey [6]. Also, certain age groups receive more medical attention than others [58], and different ethnic backgrounds use westernized medical care to varying degrees [59,60].

Fibromyalgia in the general population The best estimates of prevalence of disease within the general population obviously result from general population surveys. Similarly, estimating changes in disease incidence over time requires either incidence studies prolonged over many years, or consecutive surveys within a fixed general population that are adjusted for changes in population demographics. Although several general population surveys now have been published, there are no published reports that a given population has been studied more than once. The only reported incidence study was limited to females aged 26 to 55; this study was not long or large enough to address the issue of increasing incidence over time [61]. Hence, to date, there are no data supporting the hypothesis that FM incidence or prevalence is increasing in the general population. The first general population study of FM reported in the English medical literature appeared in the Scandinavian Journal of Rheumatology in 1989 [62]. Over the next several years, numerous additional general population surveys were performed, generally demonstrating a general population prevalence of FM between 0.5% and 5% (Table 2) [16,63 66]. In studies published prior to 1990, the investigators obviously could not use the 1990 ACR criteria, which limits comparison of earlier and more recent studies.

Only three of these community surveys have gone substantially beyond just estimating FM prevalence; each of these three surveys attempted to address the clinical characteristics and costs of FMS. In 1993, Prescott et al. [67] reported the results of a survey of 1219 Danish adults aged 18 to 79 years. Examinations were performed on 65 of 123 individuals screening positive for widespread pain, confirming FMS in eight females. The estimated minimum prevalence of FM was 0.66% [67]. Although the absolute number of confirmed FM cases (N = 8) was too small to analyze for demographic and clinical characteristics, the investigators divided the 44 examined females (males were excluded to eliminate sex as a potential confounder) into three groups, based on their fibromyalgia tender point count: 1) 0 to 4 points, N = 22; 2) 5 to 10 points, N = 14; and 3) 11 or more points, N = 8. Having more tender points was associated with a higher score on a pain index, more subjective swelling, worse fatigue, more frequent headaches, a perception of worse overall health, and greater difficulty climbing up stairs [68]. In 1995, Wolfe et al. [3] reported on the results of a mailed survey of 3006 adults aged 18 and older living in Wichita, KS. From this sample, 193 individuals with CWP were examined and 36 cases of FM confirmed; the sex distribution of cases was not reported. The age and sex-adjusted prevalence of FM was estimated at 2.0% overall (95% CI 1.4% to 2.7%), 3.4% in women (CI 2.3% to 4.6%) and 0.5% in men (CI 0.0% to 1.0%). In females, FM prevalence appeared to increase steadily through the eighth decade, then fall; prevalence in males similarly peaked in the eighth decade, but only at just above 1%. Notably, however, CIs for these estimates were not given. Given the relatively small number of confirmed FM cases, especially among males, agespecific confidence limits likely would be too broad to permit conclusions regarding FM prevalence and age. Demographic and social factors associated with the presence of FM in the general population were female sex, being divorced, failure to complete high school, and low household income [3]. Clinical factors associated with FM were decreased pain threshold on dolorimetry testing, pain all over, subjective joint swelling, paresthesias, morning stiffness of greater than 15 minutes duration, sleep disturbance, fatigue, irritable bowel syndrome, moderate or severe impairment on the Health Assessment Questionnaire, increased pain, fair and poor self-reported health status, and moderate and marked dissatisfaction with health. Psychological factors associated with FM included somatization, anxiety, depression, increased global severity of psychiatric illness, history of past or current depression, prior hospitalization for depression, current depression, and family history of depression. With respect to health service utilization and disability, a greater proportion of persons with FM versus persons without had visited a physician in the previous 6 months and had applied for disability benefits, but there was no significant difference with respect to current analgesic use [3].

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Table 2. The prevalence of fibromyalgia in general populations

Prevalence estimate

Fibromyalgia

Study 876 7217 438 1102 1105 2425 1219 3006 3395 18+ 18+ 193 176 36* 100 3.4 4.9 0.5 1.6 5070 30+ 2574 35+ 18+ 2074 16+ 80 110 147 65 9 54 10 35 8 1.8 1 5.5 0.2 0.5 0 0

Country

N Age range, y Females, % Males, %

Subjects with Fibromyalgia cases CWP examined, n identified, n

Overall, % 1 0.8 2.3 3.2 4.5 1.3 0.7 2 3.3

Arnett et al. [35] Hadler [36] Coderre et al. [37] Kwiatek et al. [38] Gagliese and Katz [39] Epstein and Henke [40] The American Rheumatology Committee [41] Mazanec [43] Campbell et al. [45] USA Canada

Sweden Finland Germany South Africa Poland Sweden Denmark

* A total of 18.9% of 193 subjects with CWP. CWPchronic widespread pain.

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Figure 1. The general population prevalence of fibromyalgia in females.

In 1999, we published results of a similar general population survey of 3395 noninstitutionalized adults who had been selected randomly and screened for CWP; 248 screened positive and 176 were examined [6]. One hundred community cases of FM were identified, yielding an overall age- and sex-adjusted FM prevalence of 3.3% (CI 3.2% to 3.4%); 4.9% in females (CI 4.7% to 5.1%) and 1.6% in males (CI 1.3% to 1.9%). Because of the relatively large number of FM cases confirmed among females (86), confidence limits were presented for each age-specific prevalence estimate, which showed a statistically significant increase in FM prevalence in women, peaking near 10% in the 55 to 64 age group, then steadily declining. Males showed a similar age-prevalence curve, but CIs were broad, given only 14 confirmed male cases. The age-specific prevalence rates for females in both the Wichita [3] and London [6] studies are presented in Figure 1 and are remarkably similar, with one notable difference. Both studies show a much lower prevalence of FM in younger women than was reported in Arendal, Norway [69]. Also, as with the Wichita study, demographic and social factors associated with FM were female sex, failure to complete high school, and low household income. Being divorced was associated with having CWP, with or without FM [6]. Compared to the 76 with chronic widespread MSK pain who failed to meet the FM case definition, the 100 confirmed patients with FM reported more severe pain and fatigue as well as more symptoms and major symptoms, and worse overall health [32]. The most commonly reported major symptoms among patients with FM were MSK pain, fatigue, severe fatigue lasting 24 hours following minimal activity, nonrestorative sleep, and insomnia. Subjects with CWP and 11 to 14 tender points were more clinically similar to those with 15 to 18 tender points than to those with 7 to 10 tender points. Compared to the widespread pain controls, patients with FM spent more days sick in bed, were more likely to have had to reduce their work time due to health, were more likely to claim being

totally disabled (31% vs 11%), and were more likely to be receiving a disability pension (26% vs 9%) [31].

Associated conditions and potential risk factors To date, there are very limited data with respect to risk factors for developing FM, other than female sex and age. A family history of FM may increase risk [70,71]. A number of illnesses appear to commonly coexist with FM. Up to 65% of rheumatology clinic patients with primary systemic lupus erythematosus meet the ACR criteria for FM [72], and FM appears to be a common component of rheumatoid arthritis [73] and osteoarthritis [74]. Such reports have led some to speculate that FM is, itself, an autoimmune disease; to date, however, data tend to refute that theory [75]. Men and women who are infected with HIV [76] and women with hyperprolactinemia [77] or thyroid disease [78] appear to have a significantly increased risk of FM. Women with hyperprolactinemia have a risk that is 15 times as great as women without. Males with sleep apnea may or may not have an increased risk of FM [79,80]. Despite the apparent associations between FM and various comorbid illnesses in clinic case-control studies, there are very limited data on the frequency of comorbid illness in individuals with FM in the general community: we found that nine of our 100 FM cases had hand evidence of rheumatoid arthritis (versus zero of 76 pain controls), and 22 had hand evidence of osteoarthritis (versus 36% of controls) [31]. Because FM appears to be relatively common, it may be that comorbid illness only affects a small percentage of the total FM population. Is trauma a risk or causative factor for fibromyalgia? An estimated 25% of FM study subjects recall some event that immediately preceded the onset of their FM symptoms; most often that event is physical trauma [78]. This trauma can be either major, as in a motor vehicle collision or fall, or minor, as in the repetitive trauma that may occur in the work place. Bennett [81], Greenfield [82],

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Fibromyalgia

Table 3. Long-term prognosis in fibromyalgia

Study Kennedy and Felson [91] Bengtsson and Backnman [92] Ledingham et al. [93] Granges et al. [94] Felson and Goldenberg [95] Papageorgiou et al. [97] N 29 49 72 44 39 79 Setting Specialty clinic Specialty clinic Specialty clinic Specialty clinic Specialty clinic General population Female, % 86.2 90.3 84.1 84.6 94 Mean age (range), y 43.5 () 52 (1881) 35.7 (1561) 44.1 () 48.6 (2486) Follow-up, y 10 8 4 2 2 1.5 Remissions*, % 0 "rare" 2.8 24.2 0 6.3

* Remissions defined as resolution of chronic widespread pain.

Romano [83], and Waylonis and Perkins [84] all have characterized posttraumatic or reactive FM. Bennett [81] has claimed that FM symptoms, if they are to occur, can develop between 6 and 18 months following a traumatic event [81]. Greenfield [82] and Waylonis and Perkins [84] note that patients with FM whose onset has been traumatic usually have a worse outcome. However, there are many critics of the concept of posttraumatic FM, some of whom are quite vocal [85,86]. Until recently, there was no convincing evidence either to support or refute an association between trauma and FM [87]. In 1997, Buskila et al. [88] published the results of a study showing a 21.6% incidence of FM among Israeli adults in the first year after suffering a neck injury. A more than 40fold increase in expected FM incidence is difficult to justify on the basis of experimental error [54]. Nonetheless, further studies are required to verify these results, and to assess the effect of other forms of trauma on FM incidence [89]. Moreover, it is possible that factors other than the trauma itself, such as the injured individuals pre-accident level of health, may have important causative roles [90].

Natural History of Fibromyalgia

What happens over time? Studies generally indicate that complete remissions of FM, with complete resolution of chronic pain, are rare. Nonetheless, there may be reason for limited optimism (Table 3). In the longest follow-up study, a 10-year, prospective study of 39 clinic patients with FM in Boston, MA, there were no cases of complete remission, with all subjects reporting some FM symptoms at the studys end [91]. Moderate to severe pain or stiffness was still reported by 55%, moderate to severe sleep difficulty in 48%, and moderate to extreme fatigue in 59%. However, 66% felt they were a little to a lot better than when first diagnosed, 55% felt well or very well, and only 7% felt poorly. In an 8-year Swedish study of 49 patients with FM, remissions were described as rare [92]. In a 4-year British study, 97% of 72 patients had continued symptoms for the duration of observation [93]; in this study, 60% were worse and only 26% improved versus baseline.

A more optimistic clinic picture was presented in a 2year Australian study of patients with FM not receiving compensation, in which almost half of the subjects no longer met the case definition for FM at the end of the study; however, this study did not use current criteria for FM [94]. In the clinic, patients with FM who appear to have the most favorable prognosis are younger females presenting with milder disease [95] and children [96]. The London, Ontario group presented 18-month follow-up data on 79 confirmed FM cases from the community (hence, potentially nonpatients); 16 of 79 (20%) no longer met the full case definition for FM at 18 months, but only five no longer had CWP, of whom three had had complete resolution of pain (Poster presented at the 12th Pan American Congress of Rheumatology, Montreal, Quebec, 1998). The London prevalence study also discovered a significant decrease in the prevalence of FM in elderly females [6]. This differs from the Wichita study [3], in which the prevalence did not drop until the ninth decade; recall, however, that confidence limits were not presented with the Wichita data, so the apparent rise through the eighth decade may be an artifact. A decline similar to the London study already has been reported in the prevalence of chronic low back pain [97]. If, in fact, the prevalence of FM does begin to decline after the 55 to 64 age group, one must ask why, because FM generally has been regarded to be a noninfectious, chronic, nonremitting, noncrippling, and nonfatal disorder [87]; as such, the prevalence would be expected to rise throughout life. There are at least three potential explanations for the observed age effect. The first is that FM does remit, particularly in individuals over age 64. Although studies show remissions to be rare in FM, many subjects with FM did have resolution of some of their pain over time, and may no longer report the CWP for which the London investigators screened. A second explanation is selective mortalitythat individuals with FM are more likely to die than age- and sex-matched individuals in the general population. FM could have a potentially fatal course itself, it could be a confounder through association with other, potentially

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fatal illnesses, or it could reduce survival in other conditions. As stated earlier, clinic studies already have demonstrated that FM commonly coexists with lupus [72] and rheumatoid arthritis [73], diseases with a standardized mortality ratio greater than one. A third hypothesis is that the differences across age groups reflect different years of birth (a cohort effect) rather than an age effect per se. Sometime in the past, there may have been an epidemic of FM, specific to one particular age group. If FM truly is chronic, nonremitting, and nonfatal, then this peak of FM prevalence would follow this cohort as it ages. Further study of larger samples would permit a more accurate estimation of age, period, and cohort effects. Allowing for this possibility, then the epidemic of FM must be explained, and the potential especially for an infectious or other environmental cause must be re-examined.

Conclusions
Some authors argue that the label of FM is harmful; that the process of labeling a patient with the FM diagnosis, in itself, creates illness behavior and disability, and hence a poor clinical outcome [98,99]. Hadler [100] has made a case for the risks of labeling, citing black lung disease in the coal mining areas of the United States. There also is evidence in patients with FM that the degree of concern a patient has about their health is an independent predictor of their overall level of disability [101]. Recent data argue against this negative effect of labeling, however. At an 18month follow-up assessment of 58 female community cases of FM, all of whom had received the FM label for the first time at study entry, there was no significant worsening in pain, fatigue, or any other symptom over time [102]. Data from the 36-month assessment are even more encouraging (White, Unpublished data).

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: Of importance Of major importance
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