Introduction

Chronic musculoskeletal pain is a very common symptom. It can be conveniently divided into two categories for the purpose of epidemiological studies. Chronic widespread pain (CWP) means pain present every day for at least 3 months, in sites on both sides of the body, both above and below the waist as well as in the spinal region. Chronic regional pain (CRP) means pain present every day for at least 3 months which does not fulfil the definition of CWP. For example, pain confined to one arm or to one arm and one leg on the same side of the body. However, it is important to remember that these definitions do not separate groups that have clinically distinct illnesses. Also, individuals can move from having CWP to CRP and vice versa.

Within the definition of CWP lies the phenomenon fibromyalgia (FM) (Wolfe et al 1990). Equally, joint hypermobility syndrome (JHS) (Chapter 1) may present as widespread pain of a chronic nature, or indeed as regional pain.

Both FM and JHS are considered to be relatively common in the general population. Joint hypermobility (JHM) is very common. It is not surprising therefore that FM and JHM may occur in an individual by chance. Whether they are mutually exclusive or appear together by pathogenic association is open to debate. There has been no large-scale general population epidemiology study of either FM and JHM or FM and JHS published to date. What has emerged from several small studies is an apparent association between FM and JHM.

Perhaps most compelling in the argument that FM and JHS might share pathophysiological mechanisms are the findings of psychosocial symptoms, sensitization of the nervous system to pain and autonomic disturbance, common to both. However, it is highly plausible that these pathologies may be a consequent response to the presence of CWP rather than represent disease processes with specific mechanisms directly related to FM or JHS.

This chapter introduces CWP, then the history behind the concept of FM, and finally will examine the association between FM, JHM, JHS and autonomic dysfunction.

Chronic widespread pain

Prevalence

From large population surveys the prevalence of CWP is approximately 11% and CRP 25% (Croft et al 1993, Bergman et al 2001). Bergman’s community study of over 1800 people in southern Sweden over a period of 3 years demonstrated that these figures were constant over time in this population but that individual’s pain patterns changed. It was noted that 76 individuals went from CRP to CWP and 64 moved in the other direction. Furthermore 222 moved from having no chronic pain to either CRP or CWP while 201 moved from CWP or CRP to no chronic pain (Bergman et al 2002).

CWP is a symptom, not a disease. That it truly is common in the general population without having identified disease or bias by focusing attention on those who seek health advice is perhaps best seen in the study carried out by Wolfe et al (1995) in Wichita, Kansas. Here, a postal questionnaire about pain was sent to households selected randomly from a directory of addresses. Among 3000 individuals who returned data, the prevalence of CWP was 10.6% and that of CRP, 20.1%; remarkably similar to earlier studies.

Given that JHM has a population prevalence of greater than or equal to 10% one can see, even without association, that there is at least a 1 in 100 probability (1%) of identifying both CWP and JHM in any one individual by chance. Large-scale population studies would be required to identify the true degree of linkage.

Patients with CWP often have poor health and reduced quality of life. Croft et al (1993) showed strong associations between the presence of CWP and fatigue and depression. A number of other studies have looked at the factors that influence development and/or persistence of CWP (Buskila et al 2000, McBeth et al 2001a, 2001b, Bergman et al 2002) and have shown that many of these factors are psychosocial and not related to any particular organic or physical process that causes the pain. This does not mean that the pain suffered by patients with CWP is any less real and distressing than that suffered by patients with, for example, rheumatoid arthritis or osteoarthritis.

In general, it is thought that most CWP arises from soft tissues such as muscles, that otherwise appear normal on examination or scans. Thus, unlike diseases in which inflammation of a particular tissue or tissues is known to be the proximate cause of the pain there is often no physical or clear physiological cause for CWP, a phenomenon common to FM.

Fibromyalgia

Developing the concept

The fact that many patients present with widespread pain apparently emanating from soft tissues, but with no specific or readily diagnosable cause, has been recognized for many years. The clinical picture has been given various names, including fibrositis. In the mid 1970s, Moldofsky et al (1975) carried out electroencephalography (EEG) readings during sleep in patients with this clinical picture, and concluded that they showed a specific pattern – the alpha-delta pattern. It was also reported that a similar pattern could be induced in healthy adults who were deprived of non-rapid-eye-movement sleep and proposed that it might result from abnormalities in serotonin balance in the brain (Moldofsky & Scarisbrick 1976). They termed chronic pain with sleep disturbance and alpha-delta EEG pattern ‘fibrositis syndrome’. Others were to use the term FM to describe such patients. There was, however, no universally accepted definition for FM, making it difficult to carry out robust prevalence studies or clinical trials.

Thus, in the late 1980s, the American College of Rheumatology (ACR) assembled a multicentre group to carry out a study to establish diagnostic criteria for FM (Wolfe et al 1990). The group reached consensus as to which clinical data should be gathered from each subject in the study including the sites at which the soft tissues should be palpated for tenderness. It emerged that two criteria were necessary to make a diagnosis with a sensitivity of 88.4% and specificity of 81.1%. These criteria were:

• CWP – as defined above

• At least 11 tender points out of 18 sites as defined on a body map (Figure 5.1).

Although other symptoms, notably sleep disturbance and fatigue were reported commonly by patients with FM, adding them to these classification criteria did not improve either specificity or sensitivity. It was also recognized that there were no blood tests, scans or histopathological findings with either specificity or sensitivity for FM.

Wolfe et al in the 1995 Kansas questionnaire study on CWP invited subjects to attend for physical examination where the number of FM tender points was assessed. Of 193 subjects examined, 25.2% of the women and 6.8% of the men had 11 or more tender points and therefore fulfilled the definition of FM. This equated to a point prevalence of 2% with a clear gender difference of 3.4% in women and 0.5% in men. It is intriguing to note that the ratio of women to men (approx. 3:1) is remarkably similar to that of JHM in the general population.

Fibromyalgia: The size of the problem

Once thought to be a nearly random assortment of unverifiable signs and symptoms, FM has emerged as a diagnosable and regrettably common disorder. It is recognized by the American College of Rheumatology (ACR), U.S. Social Security Agency, U.S. Veteran’s Administration, U.S. Federal Drug Administration (FDA), European Medicines Agency (EMEA) and the World Health Organization (WHO). Given a prevalence of 2% in the United States, 4.7% in Europe (Branco et al 2008) and increased awareness worldwide, FM is now a major health burden for both the individual and society at large (White et al 1999, Penrod et al 2004, Berger et al 2007, Hoffman & Dukes 2008). In 2005, the cost of FM per patient ($10,199/year) was nearly equal that of osteoarthritis (White et al 2008).

In a British group of 72 patients with FM followed for a median of 4 years, 97% continued to have symptoms of pain, tiredness and/or lethargy, 85% still had multiple tender points and 60% felt worse at follow-up than at presentation (Ledingham et al 1993). Half the patients had stopped work due to their illness and 32% described themselves as being heavily dependent. These results are consistent with those of other groups. Wolfe et al (1995) showed that there was a strong correlation between FM and applications for disability benefits, and 62% of a Swedish population with FM required such benefits (Burckhardt et al 1994). In a large study using records from the United Kingdom General Practice Research Database, Hughes et al (2006) compared 2260 patients with a recorded new diagnosis of FM with non-FM controls (ten controls per case). They found that patients with FM had significantly higher rates of clinical visits, prescriptions and diagnostic tests than the control group from at least 10 years prior to the diagnosis being made.