Introduction

International interest in fibromyalgia (FM) arose around 1980. A number of criteria sets, all generally similar in that they were based on some combination of tender points (TP) and symptoms, were proposed. The American College of Rheumatology (ACR) 1990 criteria are now the most widely used. The two operational criteria are chronic widespread pain (CWP) defined as pain in all four quadrants of the body and the axial skeleton for at least 3 months, and the finding of pain by 4 kg pressure on digital palpation of at least 11 of 18 defined TP sites [1]. The criteria have not been further validated [2].

Fibromyalgia is a medically unexplained condition with a reported prevalence of mostly about 2–3%. Up to about 25% of patients correctly diagnosed with a systemic rheumatic disease, e.g. rheumatoid arthritis and systemic lupus erythematosus will also fulfil the FM criteria [3].

Several auxiliary symptoms that are not required for the FM diagnosis include sleep disturbance, fatigue, anxiety, prior depression, paresthesias, headache, irritable bowel and urinary urgency [1]. FM and the auxiliary symptoms demonstrate a substantial degree of overlap and co-existence with other unexplained conditions, and similarities in formal case definitions are unlikely to account for most of the overlap. It is reviewed that twelve such conditions for which published criteria exist include chronic fatigue syndrome (CFS), regional myofascial pain syndromes, irritable bowel syndrome (IBS), interstitial cystitis, tension and migraine headache, chronic whiplash syndrome and premenstrual syndrome [4, 5].

The syndromes are often referred to as functional somatic syndromes (FSSs), the term “functional” suggesting an alteration of function rather than of structure. They share a strong female predominance and are generally worsened by stress [6, 7].

It is suggested that FSSs would be better understood if they were considered together [6, 7]. Most of them are defined in ways that do not exclude co-existent FM [4, 5]. In FM, on the other hand, are listed as auxiliary symptoms what may be clues to other FSSs, which does not open for a common evaluation.

The aim of this review is to provide a survey of the FM criteria and to discuss whether FM should be considered as a rheumatic condition.

CWP

Chronic widespread pain affects 10–12% of the general population. Risk factors for persistent CWP are female gender, older age, fatigue, depression, somatization and distress [8–10]. The prognosis of pain is good for individuals who do not display features of somatization and have few other risk factors [8].

The term “distress” can be defined as symptoms that cannot be ignored or stop subjects from doing things, in relation to minor nuisances one will not care for, and is operationally some combination of somatic symptoms and symptoms of anxiety/depression [7, 11].

Most individuals or about 60% reporting CWP have <11 TP [12, 13]. The diagnostic and other clinical information that should be given them when they present for medical care is unclear. They are hardly a parallel to the 12% of false-negative patients from the ACR study that in a consensus in the mid-1990s could be given the FM diagnosis, provided the presence of CWP and many auxiliary symptoms, which was also a reversion to criteria sets proposed in the early 1980s requiring <11 TP [1, 2]. Instead, these 60% of individuals challenge the diagnostic value of TP, and they can only be given an unspecified symptom diagnosis.

TP

The TP examination requires personal experience and evaluation [1] and is therefore, by definition, no objective investigation. Initial findings in FM from the 1950s of abnormal muscle energy metabolism seemed confounded by subtle metabolic changes resulting from muscle deconditioning, both at TP and non-TP locations, and were also excluded by MR spectroscopy. Findings of low muscle strength and function could be explained by lack of voluntary effort. Other suggestions of excessive muscle tension leading to increased excitability of nociceptors in muscle, muscle hypertension and chronic pain, or defective sympathetic nerve control that resulted in disturbed microcirculation and nociceptor excitation were ruled out by EMG techniques [14]. Despite renewed interest in potential abnormalities of energy metabolism in muscles of FM [15], it is generally agreed that FM is no primary disorder of muscles or peripheral tissues and that TP are no measure of musculoskeletal engagement.

The latter is supported by the finding that pressure tenderness in FM is not confined to the TP but, instead, extends throughout the entire body [16]. The tenderness is therefore characterized by widespread hyperalgesia or probably more correctly by widespread allodynia, i.e. pain in response to normally non-painful stimuli. Characterizes FM by diVusely increased perception of pain. FM patients can therefore be diVerentiated from controls by testing their pain threshold anywhere on the body, not just the TP

There is considerable evidence that the TP are simply body locations in which everyone is generally more tender. In FM they are more tender than normal for pressure as well as for heat, cold and other sensory stimuli due to decreased pain threshold. Thus, FM patients cannot detect pressure and other sensory stimuli at lower levels than normal, but the point at which the stimuli bring about pain or unpleasantness is lower [16–18].

Pain threshold

Overall, a decrease in pain threshold and tolerance appears as the most consistent and objective finding in FM and other FSSs [4]. Pain threshold is lower in women than men, and women are about ten times more likely to have 11 TP than men. The TP requirement in the FM criteria together with a higher prevalence of CWP and distress in women cause FM to become almost exclusively a female disorder, and rather affecting middle-aged than younger women [10, 19, 20].

Thus, excluding the TP criterion in FM would lead to a different disorder: one that affects far more men with higher pain threshold, with the group displaying lower levels of distress.

Trigger points

Trigger points (TrP) can be defined as a focal tenderness in a taut band of skeletal muscle, which produces referred regional pain (zone of reference) and a local twitch response. They are characteristic for myofascial pain syndromes like temporomandibular disorder where pain is usually more regional. Myofascial TrP is possibly a spinal reflex disorder but the pathogenesis remains unproven.

Although there is no such thing as FM TrP, the TrP may be confused with TP because FM is often associated with myofascial pain syndromes and more widespread myofascial pain [4, 5, 21].

A tender subject

Pressure pain represents a phenomenon different from the actual reporting and expression of pain. Hence TP mostly provide symptoms only when they are examined and are in any event a secondary phenomenon to the pain [16–18].

It is therefore not the TP that may cause functional impairment and disability in FM, but the symptoms. TP cannot capture psychosocial and distress features or the many other symptoms. The TP criterion has made the impression of FM almost as a physical illness, an impression that is maintained by the many pictures of a woman with dots of TP superimposed. First author of the ACR criteria publication has even advanced the possibility of a mistake of having TP as a criterion [22].

Hence there arises the question whether FM according to ICD-10 should be listed as unspecified soft-tissue rheumatism.

FM is no discrete clinical entity

The TP count increases with larger pain distribution, but is separately associated with symptoms of distress [12, 13].

High TP counts are also associated with the extent of unspecific bodily complaints in the absence of chronic pain, and 11–18 TP can be predicted by the presence of a high score of somatic symptoms other than pain [23].

The relation between distress and TP count was studied by using a distress index constructed from five appropriate symptom variables: anxiety, depression, sleep disturbance, fatigue and global severity [24, 25]. A linear relation existed between the distress index and the entire range of 0–18 TP, with no discrete enhancement or perturbation of the index or single symptom variables at 11 TP or in the range of 11–18 TP [25].

In these studies was concluded that FM is no discrete clinical disorder [12, 13, 23, 25].

Objections to the FM criteria

Expert guidelines form the diagnostic criteria standard for FSSs or medical conditions lacking biomarkers [3]. ACR has stated that diagnostic guidelines must be reviewed periodically to ensure that they remain current or determine that revisions are warranted by new developments in the field [26].

Despite lack of information on whether the ACR criteria for FM have undergone such review, it has been argued that they should be revised or that FM should be considered together with other FSSs [6, 7, 23, 25, 27]. The recommendation of a rheumatologic FM consensus of further studies on the relationships between FM and CFS [2] seems inadequately followed up.

It is also proposed to exclude the TP criterion and regard the condition as one idiopathic CWP syndrome [27]. This syndrome should in case affect 10–12% of the general population [8–10], and provide a diagnosis to the about 60% of individuals with <11 TP when they seek medical care [12, 13]. The diagnosis should be equal to FM as regards treatment options, disability compensation and other social privileges. Optimism may also exist in using questionnaires to identify somatization features of CWP and alleviate them by means of appropriate cognitive behavioural therapies, thereby preventing the permanency of pain [8].

It is yet uncertain if some of these objections will have practical consequences, and the literature gives little doubt that FM will still be diagnosed. The diagnostic method may change, however, as recently shown by using a suitable symptom survey that does not require TP [28]. The ACR criteria publication has also the request of comparisons with other possible criteria [1].

Distress questionnaires

There are until now no simple questionnaire that can be used for symptoms of distress, and eventually replace TP. The aforementioned distress index is not restricted to rheumatology, but is some difficult and more suited for research [24]. The simple and user friendly “Fibromyalgia Impact Questionnaire” and other simple questionnaires have weaknesses in covering distress symptoms [29, 30].

FSSs and medical specialities

Each FSS has a certain characteristic that relates to a medical speciality. The result is often that the speciality has advanced some sort of a claim of the syndrome. Therefore, FM with the TP has mostly remained in rheumatology, CFS in infectious medicine and neurology, chronic whiplash syndrome in neurology, IBS in gastroenterology, premenstrual syndrome in gynecology, etc.

This does not mean that patients with FSSs belong more in speciality- than in primary health care. Many will probably be best served by a common evaluation across medical specialities [6, 7].

Neurobiology of FSSs

It is generally agreed that abnormal central nervous system (CNS) mechanisms are responsible for the majority of symptoms of FSSs. The hypotheses concern an elevated ratio of excitatory neurotransmitters like substance P (SP) and other tachychinins to antinociceptive neurotransmitters like serotonin and noradrenalin, changes in the PHA axis, neuroendocrine and autonom dysfunction, and altered serotonin neurotransmission [27, 31–34].

The levels of SP in cerebrospinal fluid (CSF) of FM are significantly increased, whereas those of the principal metabolites of noradrenalin (norepinephrine) and serotonin are lowered. Both increased SP and lowered noradrenalin and serotonin in descending, pain-inhibitory pathways at the dorsal horn of the spinal cord have been proposed as possible mechanism for causing the widespread hyperalgesia and allodynia associated with FM [27, 31].

In relation to FM, the CSF levels of SP show nearly the same elevations in major depression and a post-traumatic stress disorder with overlapping depressive symptoms. In the stress disorder, provocation of psychological stress results in a further significant SP increase [35]. The significance of this is yet unclear.

Both in FM and depression has been found low CSF levels of the principal serotonin metabolite and low serum levels of serotonin and its precursor tryptophan. In depression but not in FM are these changes accompanied by an altered uptake and transport of serotonin in platelets, which are the main source of serotonin in blood [31, 36–38]. Despite the not uncommon co-morbidity of depression and chronic pain, it may for these and other reasons appear that defective synthesis or metabolism of serotonin is more related to depression than to FM. Potential serotonin abnormalities in FM are also difficult to explain by drug treatment, which suggest that tricyclic antidepressants that increase central serotonin levels are more effective in reducing pain and other symptoms as compared to selective serotonin reuptake inhibitors and dual serotonin/noradrenalin reuptake inhibitors [39].

An up-regulation of cerebral serotonin receptors has been implicated in CFS, in contrast to the hyposerotoninergic state of major depression [32, 33, 36]. In IBS, autonomic dysfunction may cause smooth muscle dysmotility, whereas a more regional neurogenic inflammation may result in release of excitatory neurotransmitters like SP and increased visceral nociception. Similar mechanisms may occur in interstitial cystitis. The levels of SP are normal in CSF of CFS, and appear moderately elevated in painful osteoarthritis. SP has also been implicated in other FSSs like myofascial pain syndromes [31, 40–42].

Nevertheless, the hypotheses have not provided some breakthrough in treatment, and the FSSs are still medically unexplained. A better understanding of biopsychosocial mechanisms may probably be obtained if they are studied together.

The most striking similarities between FSSs are probably an underactive and blunted “stress response”, with a decreased ability of both the neuroendocrine and autonomic nervous system to respond to physiologic stressors and inciting or aggravating events like physical or emotional trauma, infections, and to stop with unstressing aerobic exercises. In polygenetic predisposed individuals, this may cause an exhausted autonomic nervous system, which is suggestive of an elevated resting cholinergic tone, and together with low HPA axis activity lead to the fatigue and mood disturbances that characterize FSSs. However, the mechanisms resulting in the more general symptoms of FM and CFS and more organ-specific symptoms of for instance IBS and premenstrual syndrome remain unclear [27, 31, 32, 43–47].

Treatment

The neurobiologic and other similarities between FSSs are reflected in similar treatment options, e.g. psychological or cognitive-based therapies, exercise treatments, and medication with antidepressants or other neuromodulatory agents [5, 6, 31, 32, 39]. No drug treatment is to date specifically approved for any FSS.

A recent FM research agenda promoted the possibility of criteria revisions in order to meet the need for optimal outcome measures. The TP count was suggested to be useful as an entry criterion in treatment trials, but less suited as an outcome measure due to the uncertain underlying pathophysiology [48].

New treatments are generally first studied in FM, and a treatment that is effective should be considered for testing in other FSSs. As yet appears that no treatment can claim to provide better results in FM than in other FSSs.

FM is no rheumatologic disorder

Rheumatic disorders are usually described in anatomic, mechanical, or immunological terms. Therefore, to test body locations for pressure pain threshold below a certain level and find the number of locations to see how widespread low pain threshold is, with no intention to find structural, inflammatory or other abnormalities, are outside usual rheumatologic examinations. High TP counts have hardly any greater clinical importance than that of making a diagnosis. The high counts can be predicted by a high somatic symptom count alone or in combination with symptoms of anxiety/depression and will include symptoms of other FSSs but not necessarily pain. The TP criterion is even more unspecific in that individuals reporting no pain are found to fulfil it [12, 23]. However, there is no clear evidence to consider TP in its own right as a population phenomenon.

It can also be argued that CWP and the conceptual about distress are outside the domain of rheumatology. Admittedly, CWP affecting as much as 10–12% of the general population [8–10] should be regarded as a more general medical concern, not belong to a certain speciality. It should perhaps come under the multidisciplinary “International Association for the Study of Pain (IASP)”. Also, the neurobiology of FM concerns abnormal CNS mechanisms, as compared to “peripheral” mechanisms studied and treated in rheumatology. Moreover, there is generally no special rheumatologic competence in the spectre of FSSs that FM can be part of.

FSSs and the primary care physician

Patients with FM or another FSS may over time acquire several FSSs and a greater illness impact. The symptoms should be regarded as real and intentional amplification or malingering is uncommon [27, 32]. Early interventions may probably provide the best outcome, and patients with FSSs initially present to the primary health care.

Given this information, it seems natural that patients with FSSs should be considered and treated by general physicians in primary health care. They are encouraged to use a broad-based diagnostic approach with simple questions and not a number of investigations for somatic explanations that are mostly unnecessary [5, 6, 49, 50].

As for FM, rheumatologists should if necessary educate general practitioners, provide them close information about the current criteria, and else take care of the up to 25% of patients with co-existing rheumatic diseases [3].

Conclusively, TP lack validity and should be excluded. A better understanding of FSSs may come from the proposal of regarding FM as one “central” CWP syndrome [27].